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Biomedical subjects

B Johansson

Publications and source records attributed to B Johansson.

At least 487 records · Page 27Linked to original sources

Geographic heterogeneity of neoplasia-associated chromosome aberrations.

Using a database comprising 13,266 cytogenetically abnormal neoplasms, the geographic heterogeneity of neoplasia-associated chromosomal abnormalities was investigated by comparing the frequencies of characteristic aberrations in consecutive series of patients with the same diagnosis. Significant frequency differences between geographic areas were found for the aberrations +8, i(17q), +19, and an additional Ph1 chromosome in chronic myeloid leukemia (CML); -5, 5q-, and +8 in acute nonlymphocytic leukemia (ANLL); t(8;21) in ANLL-M2; t(15;17) in ANLL-M3; 5q- and -7 in myelodysplastic syndromes (MDS); t(9;22) and +21 in acute lymphocytic leukemia (ALL); t(14;18) in follicular lymphoma; -8 and -22/22q- in meningioma; and structural abnormalities of 12q in pleomorphic adenoma of the salivary glands (PAS). No geographic incidence variation was detected for -7 and +21 in ANLL; +8 in MDS; 6q- and +8 in ALL; +12 in chronic lymphocytic leukemia; 6q- in non-Hodgkin's lymphoma (NHL); t(8;14) in Burkitt's lymphoma; t(11;22) in Ewing's sarcoma; i(12p) in germ cell tumors; 1p- in neuroblastoma; structural abnormalities of 3q, 8q, and 9p in PAS; or 3p- in renal cell carcinoma. Intraregional frequency similarities between cytogenetically identical abnormalities in related tumor types were also analyzed. No significant correlations were found regarding the incidence of 5q- in ANLL and MDS, 6q- in ALL and NHL, -7 in ANLL and MDS, +8 in ANLL and CML, +8 in ANLL and MDS, +8 in ALL and ANLL, or +21 in ALL and ANLL. The findings indicate that some geographic heterogeneity of tumor-associated aberrations exists both in hematologic neoplasms and in solid tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Asia↗

Trisomy 7 in short-term cultures of colorectal adenocarcinomas.

Cytogenetic analysis of short-term cultures from six adenocarcinomas of the colon revealed trisomy 7 as a recurrent clonal chromosomal abnormality. In three tumors, +7 was the sole change. In the fourth carcinoma, two aberrant clones with simple numerical aberrations were detected; one with +7 and one with +3. Tumors 5 and 6 both displayed two completely different abnormal clones; one had numerous numerical and structural abnormalities and thus was undoubtedly representative of the cancer parenchyma, and the other had only +7. The karyotypic differences between the coexisting clones in the latter two cases seem to argue against an evolutionary scenario in which the karyotypically more complex clones have evolved from the clones carrying trisomy 7 only. Furthermore, in tumor 6 the metaphases with trisomy 7 were found in colonies of fibroblast-like cells whereas those with a large number of abnormalities grew in colonies of epithelial-like cells. The combined results indicate that mitoses with trisomy 7 as the sole chromosomal change do not represent the neoplastic parenchyma of colorectal adenocarcinomas.

Adenocarcinoma↗

Effects of doxazosin and atenolol on the fibrinolytic system in patients with hypertension and elevated serum cholesterol.

Disturbances in the fibrinolytic system have been associated with cardiovascular disease and its risk factors. In the present study the effects of an alpha 1-adrenoceptor inhibitor (doxazosin) and a selective beta-adrenoceptor blocker (atenolol) on the fibrinolytic system have been evaluated. Eighty four subjects with previously untreated mild to moderate hypertension and elevated serum cholesterol were randomized to receive atenolol or doxazosin in a double-blind study over 6 months. Tissue plasminogen activator(tPA) and plasminogen activator inhibitor (PAI-1) were measured in citrated plasma samples before and after venous occlusion before and at the end of the study period. tPA activity after venous occlusion and tPA capacity were significantly increased after doxazosin as compared to pretreatment values. The fibrinolytic variables did not change in the atenolol group. Thus, doxazosin but not atenolol, improved the activity of the fibrinolytic system in patients with hypertension and an elevated serum cholesterol level. This effect of doxazosin warrants consideration when selecting a first-line antihypertensive drug.

Adult↗

HIV-1 in Ethiopia: phylogenetic divergence from other HIV-1 strains.

Phylogenetic tree analysis was performed on selected polymerase chain reaction (PCR)-amplified and sequenced regions of the gag and env reading frames of several Ethiopian and Swedish human immunodeficiency virus type 1 (HIV-1) strains. These regions are considered to be conserved parts of the HIV-1 genome and correspond to the p7 of the core (gag) and part of the carboxy terminal of the gp41 protein of env respectively. Comparisons were made with all available HIV-1 sequences. The tree analysis showed that gag sequences from nine and env sequences from four Ethiopian strains all grouped together in separate branches distinct from all other sequenced European, North American, and African HIV-1 isolates. Thus, the Ethiopian strains seem to represent a highly divergent group of HIV-1, which might have developed during a relatively early stage of HIV-1 evolution.

Base Sequence↗

Influence of severe diabetes mellitus early in pregnancy in the rat: effects on insulin sensitivity and insulin secretion in the offspring.

We studied the influence of severe diabetes early in pregnancy on insulin sensitivity and insulin secretion in the offspring. Diabetes (blood glucose greater than 20 mmol/l) was induced in female Sprague-Dawley rats before mating. Diabetic dams were insulin treated during the second half of pregnancy (mean blood glucose 10.6 mmol/l). The offspring were reared by foster mothers. Offspring of both sexes were insulin resistant at four and seven months of age as evidenced by normal glucose tolerance after glucose (2 g/kg body weight intraperitoneally) concomitant with higher than normal rises in insulin levels. Regardless of fetal environment the male rats had higher glucose and insulin levels than the female rats. Insulin responses to glucose (27 mmol/l) in vitro in perfused pancreases were not increased by maternal diabetes, male gender or higher age. Conversely responses to 3-isobutyl-1-methylxanthine (1.0 mmol/l) were enhanced by all three conditions. The pancreatic content of insulin was only marginally affected by maternal diabetes. We conclude that severe diabetes during early pregnancy affects glucose homeostasis in the offspring primarily by diminishing insulin sensitivity and that susceptibility to this effect is not sex- or age-dependent.

Aging↗

Human fatalities caused by wasp and bee stings in Sweden.

Bee and wasp stings represent an uncommon cause of death. In a retrospective study of all fatalities due to venomous animals in Sweden during a 10-year-period, we found 19 fatalities due to wasps, 1 due to bees but none due to snake bite. This gives an annual incidence of 0.2 per million inhabitants. Most of the deceased were older than 50 years and had an underlying cardiovascular disease while previous severe reactions after insect stings were uncommon. The number of stings was not a factor of importance. Symptoms and death occurred within minutes after the sting. The autopsy findings were in most cases non-specific. Although uncommon, the possibility of a fatal insect sting should be considered in unwitnessed deaths occurring outdoors in summertime.

Adult↗

Detection of human papillomavirus infection in tissue blocks by in situ hybridization as compared with a polymerase chain reaction procedure.

Tissue blocks from 25 cases of condyloma and/or dysplasia were used for human papillomavirus typing with DNA in situ hybridization, compared with the very sensitive polymerase chain reaction. Only one of these cases was negative with both methods: a case of vaginal "koilocytosis." Polymerase chain reaction, as expected, was the more sensitive method, positive in 24 cases, with seven double infections. In situ hybridization was positive in 18 cases, with only two detected double infections. There was excellent agreement between the two methods in typing results. In all cases in situ hybridization showed a positive reaction in areas of koilocytosis and/or dysplasia.

Biopsy↗

Senile systemic amyloidosis: a clinico-pathological study of twelve patients with massive amyloid infiltration.

Hearts from 12 patients, 82-92 years old, with immunohistochemically verified pronounced senile systemic amyloidosis, were studied postmortem. Sections from the left ventricle, atrioventricular and sinus nodes and atrioventricular bundle were studied using the light microscope. The weights of the hearts varied between 310 and 870 grams. In the studied parts of the conduction system, the amounts of amyloid were considerably smaller than in the surrounding myocardium. Clinical data were taken from available case records. Eight of the patients had a history of uncomplicated congestive heart failure, but only two had been in hospital with cardiac symptoms prior to their last admission. The electrocardiogram showed atrial fibrillation in nine cases, left bundle branch block in three, right bundle branch block in two and left anterior hemiblock in one. No evidence of atrioventricular dissociation was seen and, in no case, was death considered to be due to conduction disturbances. Amyloidosis was a contributing cause of death in 7 patients, while the remaining patients died of other diseases. Amyloidosis is rarely diagnosed before death and was not suspected during life in any of our patients.

Aged↗

Dementia and cognitive impairment in the oldest old: a comparison of two rating methods.

Rates of cognitive impairment in a representative population of the oldest old (aged 84 to 90) were examined using two indicators: The Global Deterioration Scale (GDS), and a Cognitive Rating (CR) derived from performance on five neuropsychological tests. Prevalence was estimated at 25.3%, using the GDS, and 30% with the CR. The overall degree of congruence between the measures was high, with most disagreements involving mildly impaired cases. The results indicate a high degree of convergence of clinical and neuropsychological indicators. The findings also confirm high rates of impairment among the oldest old.

Aged↗

A simple purification method of squeezed krill for obtaining high levels of hydrolytic enzymes.

The raw material originating from freshly caught Antarctic krill (E. superba) was processed by centrifugation and then immediately frozen. This squeezed fluid adjusted to pH 7 was subjected to spontaneous autolysis by storing at different temperatures (20-45 degrees C) and times (10-48 h). The autolyzed material resulted in 3 distinct phases after high speed centrifugation. The intermediate phase (water-phase) was collected and concentrated by membrane filtration. The high-molecular-weight substances (greater than 10,000 Daltons) were further purified by ion-exchange chromatography and eluted by a salt gradient. In this matter a bulk enzymatic material from krill can be efficiently obtained for further purification of different hydrolytic enzymes (peptide hydrolases/carbohydrases).

Animals↗

Detection of HIV-1 DNA and infectious virus in cerebrospinal fluid.

The polymerase chain reaction (PCR) and a virus culture technique were used to detect human immunodeficiency virus type 1 (HIV-1) DNA in cerebrospinal fluid (CSF) cells and infectious virus in cell-free CSF, respectively, of 28 HIV-1 seropositive homosexual men. Provirus was detected in 24 patients of whom 15 were also culture positive. One subject was virus culture positive but not PCR positive. Two asymptomatic HIV-1 seropositive persons and one individual with persistent generalized lymphadenopathy were negative by both techniques. All of four patients with overt neurological symptoms, but also 20 of 24 patients without such symptoms were PCR positive. The data indicate that viral replication is common, and that the vast majority of HIV-1-infected individuals harbor the virus DNA in CSF, during all stages of infection.

AIDS-Related Complex↗

Increased luminol-enhanced chemiluminescence of blood monocytes and granulocytes in Hodgkin's disease.

The oxidative metabolic burst of blood monocytes and polymorphonuclear leukocytes (PMN) from 22 untreated patients with Hodgkin's disease (HD) and 18 healthy subjects were studied. Monocytes and PMN were enriched by density centrifugation and in vitro activated by zymosan. The oxidative metabolism was measured by luminol-enhanced chemiluminescence (CL). The CL of the patients' monocytes and PMN was higher than that of controls (P less than 0.01 and P less than 0.05, respectively). Patients with stage II-IV HD showed an increased blood monocyte CL as compared with stage I patients (P less than 0.05). Furthermore, patients with lymphocytic depletion or mixed cellularity subtype demonstrated an increased CL of PMN as compared with the remainder. Enhanced CL of phagocytes has been observed in chronic inflammatory disease and can be induced by various serum factors such as monokines and immune complexes. The present study demonstrates an increased CL of blood-borne phagocytic cells in untreated HD. Furthermore, CL of blood monocytes and PMN correlated to tumour burden and histologic subtype, respectively.

Adolescent↗

Hypo-fibrinolysis in patients with hypertension and elevated cholesterol.

To test the hypothesis that increased blood pressure and hyperlipidaemia result in changes in the fibrinolytic system, 84 subjects with both hypertension and elevated serum cholesterol levels (the high risk group) were compared with 55 controls matched with respect to age, sex and body mass index (BMI). Plasminogen activator inhibitor (PAI-1), and tissue plasminogen activator (tPA) antigen and activity were measured before and after venous occlusion. In the high risk group, tPA activity was significantly lower both before and after venous occlusion and PAI-1 levels were significantly higher. In a multivariate analysis the triglyceride levels, diastolic blood pressure and cholesterol levels were independently associated with the PAI-1 levels. Diastolic blood pressure was independently and inversely associated with resting tPA activity. We conclude that patients with hypertension and hyperlipidaemia have a reduced activity of the fibrinolytic system, an effect which is unrelated to differences in age, sex, smoking or BMI.

Body Mass Index↗

Mitoxantrone, etoposide, cytarabine and prednisone as salvage therapy for refractory non-Hodgkin lymphoma (NHL) and alternated with CHOP in previously untreated patients with NHL.

The treatment of relapsing or refractory high-grade malignant non-Hodgkin lymphoma (NHL) following CHOP chemotherapy remains a challenge for the clinician. In this study, 29 patients with relapsing or refractory high- or refractory low-grade malignant NHL received a combination of mitoxantrone 12 mg/m2 i.v. on days 1-2, cytarabine 100 mg/m2 i.v., b.d. d 1-2, etoposide 100 mg/m2 i.v. d 1-3 and prednisone 100 mg/m2 orally d 1-3 (ENAP). An overall response rate of 55% encouraged us to use ENAP alternated with conventional CHOP chemotherapy in 45 previously untreated NHL patients (35 with high-grade and 10 with "aggressive" low-grade malignant NHL). All patients responded with a complete remission rate (CR) of (27%) and a partial remission rate (PR) of 73% after only one course of ENAP. After a median number of 3.5 ENAP/CHOP courses, the CR and PR rate was 69 and 22%, respectively. Myelosuppression was pronounced and fever of unidentified origin and documented infections followed 59% of all cases given ENAP courses. In the last 19 previously untreated patients mitoxantrone was given at a dose of 10 mg/m2 on d 1 and cytarabine 100 mg i.v., b.d. during d 1-2. Nonhematologic toxicity was mild. We conclude that this novel chemotherapy program is effective both as first-line and salvage treatment in patients with high-grade malignant NHL. Furthermore, ENAP appears clinically to be partly non-cross resistant with CHOP chemotherapy. The dose-limiting toxicity is myelosuppression. The combination should be explored as primary therapy in combination with other chemotherapy or radiotherapy programs.

Adult↗

Cytogenetics of secondary myelodysplasia (sMDS) and acute nonlymphocytic leukemia (sANLL).

76 cases of secondary myelodysplasia (sMDS) and acute non-lymphocytic leukemia (sANLL) were cytogenetically analyzed. Among the 36 sMDS patients, 13 (36%) had only normal karyotypes whereas 23 (64%) displayed clonal chromosomal abnormalities. The most common aberrations were -7, 5q-, -5, and +8. In 10 patients (43% of the cytogenetically aberrant cases), clones with only one anomaly, mostly 5q- or -7, were found. Of the 40 sANLL patients, normal karyotypes were detected in 10 (25%). Among the 30 (75%) abnormal cases, the most frequent aberrations were -7, -5, +8, 7q-, -17, and +21. 12 patients (40%) had clones with single abnormalities, most often -7. In 4 sANLL patients cytogenetically unrelated clones were detected. A survey of all previously published secondary hematologic neoplasias reveals that the most frequent abnormalities in sMDS are -7 (41%), 5q- (28%), and -5 (11%), followed by der(21q), +8, 7q-, der(12p), t(1;7), -12, -17, der(17p), der(3p), der(6p), and -18. Clones with single aberrations have been found in 45% of the cases and cytogenetically unrelated clones have been described in 6%. The most common abnormalities in sANLL are -7 (38%), 5q- (17%), -5 (15%), +8 (13%), and -17 (11%), followed by der(3q), der(11q), der(12p), -21, 7q-, -18, der(3p), der(17p), +21, der(21q), der(6p), and -16. 38% of the sANLL patients have had clones with only one aberration and 3% have had unrelated clones. The frequencies of these nonrandom abnormalities in sMDS and sANLL are thus remarkably similar - the only exception appears to be 5q-, which is more common in sMDS. Also the mean number of abnormalities per case is similar - 5.3 in sMDS and 5.6 in sANLL. When the incidences of characteristic cytogenetic abnormalities were correlated with the type of previous therapy, -7 was found to be more frequent in sMDS and sANLL patients who had been exposed to chemotherapy whereas 5q- was associated with previous exposure to ionizing radiation in sMDS patients.

Aged↗

Dose-effect relationship of disulfiram in human volunteers. I: Clinical studies.

The aim of this study was to investigate the relation between Antabus dosage and the disulfiram-alcohol reaction (DAR) after ethanol challenge. Fifty-two healthy volunteers, 29 men and 23 women, aged 20-61 years, were treated with increasing doses of Antabuse (1, 100, 200, 300 mg) for 14 days each. At the end of each 14 days the volunteers were challenged with 0.15 g ethanol/kg body weight. Blood pressure, pulse rate, respiration rate, and symptoms such as flushing, heat sensation, nausea, vomiting, palpitations, breathlessness, and headache were monitored for the next 50 min. The volunteers left the study when they had experienced a valid DAR. A valid DAR, which was principally defined on the basis of the patients' feeling of discomfort, but for safety reasons also on the basis of unacceptable circulatory changes, was reached in 21 out of 52 volunteers after 100 mg Antabuse, in 27 after 200 mg, and in 4 after 300 mg. Most of them left the study after flushing and circulatory changes, but did not feel ill enough to be convinced that they should abstain from drinking. Ten volunteers with weak subjective symptoms, but with a valid DAR, were therefore rechallenged after the next increased dose and experienced a somewhat stronger reaction. We conclude that a daily dose of 200 mg Antabuse brings about a substantial reaction in volunteers in the presence of alcohol. The possible need for a 300 mg dose of Antabuse to prevent a patient from drinking was discussed.

Adult↗

Dose-effect relationship of disulfiram in human volunteers. II: A study of the relation between the disulfiram-alcohol reaction and plasma concentrations of acetaldehyde, diethyldithiocarbamic acid methyl ester, and erythrocyte aldehyde dehydrogenase activity.

The study was designed to elucidate the basic pharmacological and biochemical effects of the disulfiram dose (Antabus) provoking disulfiram-alcohol reaction (DAR) in 52 human volunteers after ethanol challenge. Disulfiram was given daily in increasing doses (1, 100, 200, and 300 mg) in successive 14 day periods, with ethanol challenge at the end of each period, until a DAR was achieved. Irrespective of dose (except the 1 mg dose), the DAR was always accompanied by almost complete inactivation (about 97%) of aldehyde dehydrogenase (ALDH) activity in erythrocytes, plasma concentrations of diethyldithiocarbamic acid methyl ester (Me-DDC) in the range of 8-472 nmol/l and accumulated plasma concentrations of acetaldehyde in the range of 7-197 mumol/l. In four of the volunteers, the cardiovascular effects of the DAR were recorded as a decrease in diastolic blood pressure (14-47 mmHg) and an increase in pulse rate (9-40 beats/min.), accompanied by a two- to fourfold increase in the plasma concentrations of adrenaline and noradrenaline. The enzyme kinetics of ALDH in erythrocytes were regularly analysed in eight volunteers during DSF intake. In addition to the expected decrease in oxidizing capacity, the Km values were also impaired, which suggests that the inhibitor is implicated in an active site directed reaction.

Acetaldehyde↗