Marked karyotype abnormalities in two cases of acute myelogenous leukemia

Two patients with acute myelogenous leukemia with severe chromosome abnormalities are described. The cytogenetic analysis shows the following karyotype: patient No. 1: 41,XY, ?1,?2,?4,?5,?13,?15,?17,?17,?18,?22,+5 markers; patient No. 2: 46,XY,?2,?5,?7,?13,+16,?21,?21,+5 markers. In each patient one set of double minute chromosomes was observed.     

Cytogenetically distinct leukemic cell lines displaying in vitro specific proliferative and differentiation capacities may account for early disease relapse in the blast phase of CML

The cytogenetic features and the proliferative and differentiation capabilities of blast cell fractions purified on a density gradient were studied in one patient with chronic myeloid leukemia (CML) in blast crisis, both at the emergence and at relapse of the disease. The results show that relapse was due to the appearance of a new leukemic cell line that was characterized by peculiar chromosomal, growth, and differentiation features, which seemingly accounted for early refractoriness to therapy and disease progression.     

Inhibition of animal virus production by means of translation inhibitors unable to penetrate normal cells

The correlation between virus and host protein synthesis, membrane leakiness, and virus production has been studied in vesicular stomatitis virus-infected L cells, herpes simplex virus (type 1)- and Sendai virus-infected 37RC cells. In all three systems, membrane leakiness, as measured by an altered permeability to low-molecular-weight translation inhibitors (e.g., hygromycin B), is detectable at a time when the cells are very actively engaged in virus protein synthesis. The alteration of the membrane increases as the virus life cycle goes on so that an almost total and specific inhibition of viral translation by hygromycin B is achieved late in infection. Although the overall protein synthesis is not shut off in Sendai virus-infected cells, a gradual replacement of host protein synthesis by viral translation parallels an increasing plasma membrane permeability to hygromycin B, which is also correlated with the ever increasing fraction of infected cells. These results indicate that cells actively engaged in viral protein synthesis have lost, at least partially, the permeability barrier that plasma membrane maintains in uninfected cells. The presence of hygromycin B in the culture medium significantly reduces the production of mature virus in the three systems studied suggesting that this approach may prove useful in the search for antiviral agents.     

Karyotype evolution in a case of chronic myelogenous leukemia with an unusual Philadelphia chromosome translocation,t(4;22), and an additional translocation,t(3;5)

A patient with chronic myelogenous leukemia was found, at the time of diagnosis, to have an unusual Philadelphia chromosome translocation, t(4;22) (q35;q11) and an additional previously unreported translocation, t(3;5) (q27;q22). The blastic crisis, which occurred after 14 months, was characterized by the appearance of i(17q). Ten months later, two different hyperdiploid cell lines with 50 chromosomes were found in about 20% of the metaphases examined.     

Full pancreatic endocrine differentiation in a mediastinal teratoma

In a mediastinal teratoma containing pancreatic tissue rich in islet cells, immunofluorescence studies showed a high degree of differentiation of the endocrine tissue. Insulin-, glucagon-, somatostatin-, and pancreatic polypeptide(PP)-containing cells were all consistently represented. They showed the same precise topographic distribution that is seen in normal islets (i.e., a central core of insulin-containing cells with the other cell types in a peripheral position) and that is thought to be important for the integrated function of the islets. This may explain the absence of clinical symptoms of hypoglycemia. In addition, a nonrandom distribution of endocrine cell types, with PP-rich and PP-poor areas, similar to that found in pancreatic regions embryologically derived from the ventral and dorsal anlagen, respectively, was observed. This finding suggests that the unknown mechanisms responsible for the dissimilar endocrine cell contents in pancreatic regions of different embryologic origins were operating in the teratoma.     

Gastric emptying and anxiety in chronic duodenal ulcer

The authors have evaluated in a group of patients afflicted with duodenal ulcer whether anxiety might be in some way linked to gastric emptying. The 23 patients studied were subdivided into two groups: "fast" emptiers (n = 12; t 1/2 less than 90 min) and "normal" emptiers (n = 11; t 1/2 greater than 90 min). There were no significant differences between the two groups for the following parameters: sex, age, marital status, educational level, social class, number of cigarettes smoked per day, type of treatment undergone for the duodenal ulcer and maximal acid output. Anxiety levels measured with the Q4 and QII factors of the Cattell's PF 16 were found to be the same in the two groups. The authors conclude that anxiety does not seem to be linked to gastric emptying in chronic duodenal ulcer.     

Derivative 11 marker chromosome in bladder carcinoma

Cytogenetic studies on bladder carcinomas from two patients were carried out on preparations obtained by a direct method. The chromosome mode was 49 and 55, respectively. Several karyotypic changes were found in the tumors. Moreover, the analysis of Q-banded chromosomes revealed the presence in both cases of a chromosome 11p+. These rearranged chromosomes showed a very similar banding pattern. The finding of a der(11) chromosome marker in two patients is intriguing, and suggests the possibility of nonrandom chromosome changes in bladder carcinoma, as already found in other kinds of tumors. The occurrence of chromosome #11 aberrations in tumors of the urinary tract is discussed in connection with the current theories on oncogenesis.     

Depression and anxiety associated with secondary amenorrhea

Secondary amenorrhea, when an organic etiology has been ruled out, is a considerable challenge to gynecologists and family physicians. Five of 18 patients suffering from amenorrhea were found to have major depressive disorder and four others generalized anxiety disorder. The dexamethasone suppression test corroborated clinical findings in three of the five depressed patients, but otherwise yielded low specificity. Since antidepressants may potentially reverse amenorrhea when a severe depressive state is present, the findings should alert the physician to include clinical and biologic criteria for depression in the diagnostic work-up for amenorrhea.     

Chromosomal alterations in the course of viral leukemogenesis in the rat

A cytogenetic study of 35 primary thymic lymphomas induced in rats by the Gross leukemia virus revealed the presence of widespread aneuploidies, ranging from cells with 35 chromosomes or less to triploid and tetraploid cells. Analysis by G banding revealed that chromosomes No. 1, 2, 9, 12, 18–20, X in females, and Y in males were lost preferentially; unidentified marker chromosomes of various morphology and length were present in a high percentage of aneuploid mitoses. Similar alterations were observed in preleukemic thymi from rats sacrificed 30 days after virus injection, when clinical or histologic signs of the disease had not yet appeared. In rats that were sacrificed 7 or 15 days after virus injection, chromosomal anomalies were much more limited, although significantly more abundant than in the controls. Rats that were free of tumor at 130–160 days after virus injection showed a regression of the chromosomal anomalies, suggesting that these are not irreversible and are not necessarily followed by the development of a lymphoma.     

Effects of drugs on the characteristics of cat's saccadic eye movements

Eye movements were measured in concious adult cats with 4 previously implanted electro-oculographic (EOG) electrodes. Saccade characteristics were studied after parentoral administration of amphetamines, diazepam and pentothal. Control parameters were obtained in cats before drugs administration. Pentothal increases duration and decreases maximum velocity of saccades. These observations resemble those observed in men under fatigue and in drowsy animals. A possible relation between pentothal effects and saccadic movements impairment observed in certain cerebellar neurologic diseases is discussed. Amphetamines greatly modify maximum velocity of saccades in a way similar to that observed in increased alertness states. Diazepam has a weak effect on spontaneous saccades and this is similar to that observed in animals with a little decrease in the level of alertness.     

Normal bone marrow karyotype in paroxysmal nocturnal hemoglobinuria—A cooperative European study

Sixteen patients with paroxysmal nocturnal hemoglobinuria (PNH) from five European centers have been submitted to chromosome analysis. All of them had a normal bone marrow karyotype. The associations between some chromosomally abnormal cases reported in the literature and “typical” PNH or PNH phenomenon during the course of other hematological disorders are discussed.     

Acute nonlymphocytic leukemias and dysmyelopoietic syndromes in patients treated for Hodgkin's lymphoma

The clinical, hematological, and cytogenetical features of six patients with hematological disorders secondary to Hodgkin's lymphoma (HL), are described. Three patients developed a dysmyelopoietic syndrome (DMS); three, an acute nonlymphocytic leukemia (ANLL). Chromosomal analyses showed a normal karyotype in one case and an abnormal one in five cases: one with a 53-chromosome clone, two with a pseudodiploid pattern plus hyperdiploid subclones, and two with a hypodiploid pattern. Trisomy 21 was observed in two cases, tetrasomy 21 in one case, monosomy 5 and monosomy 7 in two cases. The correlations of chromosomal changes with hematological abnormalities or clinical aspects are discussed.     

Nitric oxide synthase inhibition speeds oxygen uptake kinetics in horses during moderate domain running

Within the moderate exercise intensity domain, the speed of oxygen uptake (V(O(2))) kinetics at the transition to a higher metabolic rate is thought to be limited by an inertia of the oxidative machinery. Nitric oxide (NO)-induced inhibition of O(2) consumption within the electron transport chain may contribute to this inertia. This investigation tested the hypothesis that a reduction or removal of any such NO effect via infusion of N(omega)-nitro-L-arginine methyl ester (L-NAME; a NOS inhibitor) would speed V(O(2)) kinetics at the onset of moderate exercise. Five Thoroughbred geldings underwent four transitions to running speeds of 7 m sec(-1) (two control, C, 2 L-NAME [20 mg kg(-1)]) on an equine treadmill during which pulmonary gas exchange was determined using a bias flow system. Consistent with exercise in the moderate intensity domain, in none of the transitions was a V(O(2)) slow component elicited. The L-NAME treatment significantly accelerated V(O(2)) kinetics via a reduction of the primary amplitude time constant (C, 17.3 +/- 1.7; L-NAME, 11.8 +/- 1.5 sec, P < 0.05) concomitant with faster overall dynamics (i.e. T(50) and T(75) both P < 0.05) and a trend toward a decreased O(2) deficit (C, 6.4 +/- 0.7; L-NAME, 4.7 +/- 1.2 L; P = 0.06). These data support the notion that NO contributes prominently to the oxidative enzyme inertia and thus the speed of V(O(2)) kinetics at the onset of moderate intensity exercise in the horse.     

Seasonal changes in blood oxygen transport and acid-base status in the tegu lizard, Tupinambis merianae

Oxygen-binding properties, blood gases, and acid-base parameters were studied in tegu lizards, Tupinambis merianae, at different seasons and temperatures. Independent of temperature and pH, blood oxygen affinity was higher in dormant lizards than in those active during the summer. Haematocrit (Hct) and hemoglobin content ([Hb]) were greater in active lizards resulting in a higher oxygen-carrying capacity. Nucleoside triphosphate content ([NTP]) was reduced during dormancy, but the ratio between [NTP] and [Hb] remained unchanged. Dormancy was accompanied by an increase in plasma bicarbonate ([HCO-(3)]pl) and an elevation of arterial CO2 partial pressure (PaCO2) and CO2 content in the plasma (CplCO2). These changes in acid-base parameters persist over a broad range of body temperatures. In vivo, arterial O2 partial pressure (PaO2) and O2 content (CaO2) were not affected by season and tended to increase with temperature. Arterial pH (pHa) of dormant animals is reduced compared to active lizards at body temperatures below 15 degrees C, while no significant difference was noticed at higher temperatures.     

ATP causes glomus cell [Ca2+]c increase without corresponding increases in CSN activity

The hypothesis that an increase in intracellular calcium [Ca(2+)](c) in carotid body (CB) glomus cells will cause enhanced afferent carotid sinus nerve (CSN) activities was tested in the rat CB in-vitro with the use of extracellular ATP. ATP caused a dose dependent [Ca(2+)](c) increase in identified glomus cells. A major part of total [Ca(2+)](c) increase (2/3) was due to the [Ca(2+)] influx. The rest of [Ca(2+)](c) increase (1/3) was due to the release of [Ca(2+)] from the endoplasmic reticulum (ER) [Ca(2+)] stores, and it was inhibited by the pretreatment of cells with cyclopiazonic acid (CPA), an intracellular Ca(2+)-ATPase blocker. Suramin, a purinergic P(2) receptor membrane blocker, blocked [Ca(2+)] influx due to ATP in the presence of extracellular [Ca(2+)]. Perfusion with 5 and 10 microM ATP stimulated CSN activities in both normoxia (Nx) and hypoxia (Hx). Above that level, 100 microM ATP induced slight initial stimulation in CSN activities which were subsided subsequently in Nx and partly diminished in Hx, while 500 microM ATP completely inhibited CSN activities in Nx and Hx after a slight initial stimulation. Electrophysiological measurements of the glomus cell membrane potential in the presence of ATP (100 microM) during Nx indicated cellular enhanced outward K(+) current and hyperpolarization, suggesting potential mechanism for the inhibition of CSN activities. Thus, ATP dependent linear increases in [Ca(2+)](c) did not give rise to a corresponding increase in CSN activities, contravening the normally expected increase in CSN activities following [Ca(2+)](c) rise.     

Trichomonas vaginalis infection activates cells through toll-like receptor 4

While Trichomonas vaginalis infection can cause inflammation and influx of leukocytes into the female genital tract, the molecular pathways important in inducing these effects are not known. This study determined if infection with T. vaginalis activates cells through toll-like receptor 4 (TLR4). Genital tract secretions from infected women stimulated TNF-alpha production by cells with functional TLR4 (350 pg/ml) but significantly less by cells that are unresponsive to TLR4 ligands (44 pg/ml, P = 0.001). Secretions collected after clearance of infection also induced significantly lower responses by cells with functional TLR4 (136 pg/ml, P = 0.008). TNF-alpha responses were not reduced by Polymyxin B and did not correlate with beta(2)-defensin levels, indicating that stimulation of cells was not through lipopolysaccharide or beta(2)-defensin. These studies show that T. vaginalis infection results in the appearance in the genital tract of substance(s) that stimulate cells through TLR4, suggesting a mechanism for the inflammation caused by this infection.