A case of dysmyelopoietic syndrome with hypotetraploid karyotype

We present a patient with dysmyelopoietic syndrome and with a complex, hypotetraploid karyotype with numerous structural aberrations.     

Increased levels of spontaneous and mutagen-induced chromosome aberrations in skin fibroblasts from patients with adenomatosis of the colon and rectum

Fibroblast cell strains were established from skin biopsies taken from patients with adenomatosis of the colon and rectum (ACR) and their relatives. A total of 57 different strains (33 from patients and 24 from healthy members of ACR families not at an increased risk for colon polyposis) were tested for their frequencies of spontaneous structural chromosome aberrations, i.e., chromatid and isochromatid gaps, breaks, and interchanges. In 47 strains (27 from patients, 20 from controls), the frequencies of structural chromosome aberrations were also determined after exposing the cells to N-methyl-N'-nitro-N-nitroso-guanidine (MNNG). Both spontaneously and after mutagen treatment, the group of patient strains exhibited, on average, approximately twice the number of chromosome aberrations found in the control group. This increase was highly significant (p less than 0.001), even though there was a considerable overlap between patient and control strains. Treatment with MNNG led to a marked increase in chromosome aberrations in both patients and controls. The small differences in aberration frequencies seen between Gardner and other patient strains were clearly insignificant.     

Fine needle aspiration biopsy: A useful tool in tumor cytogenetics with special reference to malignant lymphomas

A method for chromosome analysis of malignant cells by means of fine needle aspiration biopsy has been developed. The method has some obvious advantages compared to conventional surgical biopsy. During a 1-year period 25 consecutive non-Hodgkin, non-Burkitt lymphoma biopsies from 19 patients have been studied. In 14 out of 21 lymph node biopsies chromosome analysis was successful; whereas, four biopsies of subcutaneous lymphomas were unsuccessful.     

Secondary chromosome changes in chronic myeloid leukemia: Relation to treatment

Thirty four patients with Philadelphia (Ph¹) chromosome positive chronic myeloid leukemia with clonal bone marrow chromosome aberrations in addition to the Ph¹, were divided into two groups: 1) 23 patients treated with busulfan only during the chronic phase, and 2) 11 patients treated with intensive chemotherapeutic schedules during the chronic phase. In all the material studied, about 85% of the patients showed at least one of three particular changes: +8, iso(17q), and/or +Ph¹. The frequency of each of these three aberrations was similar in the two groups. Additional structural changes of a clonal nature were, however, seen in only 3 of the 23 patients treated with busulfan only, but were present in 5 of the 11 patients treated with intensive chemotherapy. The results indicate that intensive chemotherapy may produce new stable abnormal clones in patients with leukemia. Furthermore, chromosome 1 was involved in aberrations in all 5 patients with structural changes undergoing intensive chemotherapy, but in no patient treated with busulfan only. The 11 patients treated with intensive chemotherapy were studied in Italy, whereas 20 of the 23 patients treated with busulfan only were studied in Sweden. The possibility that the differences recorded between the two groups may be geographical in nature rather than induced by treatment cannot be excluded.     

Chromosomes in neoplasia: An appeal for unpublished data

In relation to a recent survey of chromosome aberrations in 856 human neoplasms the following points are presented: 1) the chromosome aberrations of significance to the biology of neoplasms are nonrandom; 2) aberrations of a particular chromosome tend to be of similar kind; 3) aberrations cluster to a limited number of specific chromosomes; 4) geographic differences have been observed in chromosome aberrations; 5) the karyotypic pattern of a neoplasm may be influenced by previous exposure to potential carcinogenic agents; 6) the role of chromosome aberrations in neoplasia—a hypothesis; 7) a plea is made for unpublished data to be included in our next survey of chromosome aberrations.     

Determination of alternative pathway of complement activity in mouse serum using rabbit erythrocytes

Rabbit, mouse and sheep erythrocytes expressing different concentrations of membrane sialic acid were used to study possible modes of activation of the alternative complement (C) pathway in mouse, human and guinea pig serum. Mouse erythrocytes activated only human serum, whereas rabbit erythrocytes activated the sera of all three species. Based on the observation that rabbit erythrocytes activate the murine alternative C pathway a method for estimation of alternative C pathway activity (AP50 value) in mouse serum was devised analogous to that used for human AP50 determination. The method is not very sensitive to ageing or to batch variation of the indicator cells. The AP50 value of mouse serum measured by this method is of the same order as for human and guinea pig serum. Mouse serum AP50 activity is partly determined by natural antirabbit erythrocyte antibodies and is sensitive to heating (15′ at 48°C and 4′ at 56°C), and to the actions of cobra venom factor, zymosan and cysteine. Strain and sex differences with respect to AP50 activities of mouse sera were observed.     

Micronuclei in erythropoietic bone marrow cells: Relation to cytogenetic pattern and prognosis in acute nonlymphocytic leukemia

The bone marrow karyotype and the frequency of micronuclei in erythropoietic bone marrow cells (Howell-Jolly bodies) were determined in 25 adults with acute nonlymophocytic leukemia (ANLL). Ten patients had exclusively normal diploid bone marrow cells; 11 had a mixture of normal and abnormal cells, and 4 had abnormal bone marrow metaphases only. The frequency of micronuclei ranged from 3 to 28/2000 erythropoietic bone marrow cells (median 10). The number of micronuclei was significantly higher in patients with abnormal metaphases than in those with normal metaphases; in patients with a mixture of normal and abnormal bone marrow metaphases there was an association between the frequency of abnormal metaphases and the number of micronuclei. A striking difference in median survival time was found between patients with low and high numbers of micronuclei, irrespective of the cytogenetic bone marrow patterns. Patients with fewer than 10 micronuclei per 2000 erythropoietic bone marrow cells had a median survival of 148 days; those with more than 10/2000 had a median survival of only 34 days (0.002 < p < 0.02).     

Variant Ph translocations in chronic myeloid leukemia

Variant translocations were found in eight of 142 consecutive patients with Ph-positive, chronic myeloid leukemia encountered in our laboratory during the last decade. Two patients had simple, two-way variant translocations: t(17;22)(p13;q11) and t(16;22)(q24;q11). Both of these patients had an additional translocation involving chromosomes #9: t(7;9)(q22;q34) and t(9;17)(q34;q21), respectively. Complex variant translocations were found in four cases: t(2;9;22)(p23q12;q34;q11), t(3;9;22)(p21;q34;q11), t(9;12;22)(q34;q13;q11q13), and t(13;17;22)(p11;p11q21;q11). In two cases, the only discernable cytogenetic aberration was del(22)(q11). A review of the chromosomal breakpoints involved in this series and in 185 cases of variant Ph translocations previously reported in the literature reveals that a disproportionately large number of breakpoints are located in light-staining regions of G-banded chromosomes. Furthermore, the breakpoints in simple variant translocations are more often located in terminal chromosomal regions, whereas, the breakpoints in complex translocations typically affect nonterminal bands. No obvious correlation was detected between variant Ph translocation breakpoints and either fragile sites, oncogene locations, or consistent chromosome breakpoints in other malignancies.     

Chromosome pattern,occupation, and clinical features in patients with acute nonlymphocytic leukemia

Chromosome banding pattern of bone marrow cells, cell morphology according to the FAB classification, and clinical findings were compared in two groups of adult patients with acute nonlymphocytic leukemia (ANLL): 52 patients occupationally exposed to chemical solvents, insecticides, or petrol products, and 110 patients with no history of occupational exposure to potential mutagenic/carcinogenic agents. Striking differences were found between the two groups: (1) Clonal chromosomal aberrations were present in 75% of exposed patients compared with only 32% in the nonexposed group. (2) Of the patients exposed to solvents and insecticides 92% had abnormal chromosomes, whereas only 29% of patients exposed to petrol products showed abnormalities; in the total material $\text{10}\text{13}$ exposed patients with normal chromosomes were exposed to petrol products. (3) The relationship between chromosomal abnormality and exposure was evident in both females and males. However, only 29% of women with an abnormal karyotype were exposed, whereas 70% of males with an abnormal karyotype were exposed. (4) The incidence of certain characteristic karyotypic abnormalities, i.e., $\text{?5}\text{5}\text{q}\text{?}$, $\text{?7}\text{7}\text{q}\text{?}$, +8, +21, t(8;21), and t(9;22), were decidedly more common in exposed than in nonexposed patients. At least one of these changes were present in 92% of exposed patients with aberrations, whereas in the nonexposed group the incidence was only 60%. (5) The monocytic varieties of ANLL (M4 + M5) were more common in the nonexposed patients, whereas erythroleukemia (M6) was more common in the exposed group. The predominance of abnormal karyotypes in the exposed compared to the nonexposed patients was similar in leukemia types M1 + M2 and in M4 + M5. (6) There was no difference in survival time between the two groups and the same correlation was obvious in both exposed and nonexposed patients: patients who had only abnormal metaphases had poorer prognosis than those with normal bone marrow metaphases only (6 vs 1.5 months). This correlation was obvious in patients classified as acute myeloid leukemia (AML) as well as in the monocytic varieties of ANLL.     

C-band pattern in lymphocytes of patients with soft tissue sarcomas

The pattern of heteromorphisms in the C-band-positive constitutive heterochromatin of human chromosomes No. 1, 9, and 16 was studied in peripheral lymphocytes of 45 patients with soft tissue sarcomas and 78 control individuals. The parameters of the heterochromatic regions analyzed were relative size, symmetry-asymmetry within homologous pairs, and incidence of inversions. No consistent differences were found in these parameters between controls and sarcoma patients.     

C-band heteromorphism in breast cancer patients

The pattern of heteromorphism in the C-band-positive constitutive heterochromatin of human chromosomes #1, #9, and #16 was studied in peripheral lymphocytes of 54 breast cancer patients and 78 control individuals. The parameters of the heterochromatic regions analyzed were relative size, symmetry-asymmetry within homologous pairs, and prevalence of inversions. Significant differences between the two groups were found in C-band size of chromosomes #1, #9, and #16 and in incidence of inversions on chromosomes #1 and #9. Significant differences were noted between premenopausal and postmenopausal cancer patients in regard to inversions on chromosome #9 and between familial and sporadic patients in regard to C-band size on chromosome #16.     

Cytogenetic pattern in leukemic cells of patients with constitutional chromosome anomalies

Acquired karyotypic changes analyzed by banding techniques in 21 patients with a malignant hematologic disorder and a major constitutional chromosome anomaly, including ten patients with trisomy 21, five patients with a balanced translocation, and six patients with a sex chromosome anomaly. Detailed karyotypic findings were ascertained in 28 additional patients reported in the literature. Some striking differences were observed in the combined material of the present series and cases previously published as regards (a) distribution of morphological leukemia types among patients with different types of constitutional anomalies, and (b) incidence and type of acquired chromosomal abnormality among patients with different types of constitutional anomalies.     

Constitutional C-band pattern in patients with adenomatosis of the colon and rectum

The pattern of polymorphism in the C-band-positive constitutive heterochromatin of chromosomes #1, #9, and #16 was studied in fibroblasts from 23 unrelated patients with adenomatosis of the colon and rectum and in peripheral lymphocytes from 78 control persons. The parameters of the heterochromatic regions analyzed were relative size, symmetry-asymmetry within homologous chromosome pairs, and frequency of inversions. The polyposis coli patients had a significantly higher frequency (p less than 0.05) of partial and total heterochromatin inversion on chromosome #9 than the control group (37.0% compared with 21.8%). In the other parameters studied, no significant differences were found between patients and controls.     

Peptidergic (VIP) nerves in the mammalian choroid plexus

The mammalian choroid plexus was examined by immunohistochemistry and radioimmunoassay for the presence of nerves containing vasoactive intestinal polypeptide (VIP). A moderate number of VIP-immunoreactive nerve fibres were found in choroid plexuses from pig. The corresponding concentration of chemically measured VIP was approx. 10 pmol/g. VIP nerves were few in plexuses from cow, cat and rabbit and rare in plexuses from mouse and rat. Pure porcine VIP produced relaxation of isolated bovine anterior choroidal artery in vitro.     

Interactions between heart rate, psychomotor performance and perceived effort during physical work as influenced by beta-adrenergic blockade.

Effects of a single intravenous dose of propranolol (0,25 mg/kg body weight) were examined in 15 healthy male subjects who performed three reaction-time tasks of different complexity, while pedalling at five work loads on a cycle ergometer. Comparisons between measurements after propranolol and after injection of a placebo solution showed a pronounced reduction of heart rate and an increase in catecholamine excretion following propranolol. Comparisons of psychomotor performance showed no significan difference between the propranolol and placebo conditions. Nor did self-estimates of perceived physical and task-induced efforts reveal any significant effects of propranolol. The results support the notion that heart rate is not a prominent cue for perceived effort.     

Single light chain subclass (kappa chain) immunoglobulin deposition in glomerulonephritis

Renal glomerular disease characterized by the deposition of immunoglobulin light chains or monoclonal immunoglobulins was demonstrated by immunofluorescence microscopy in 11 patients. The most common histopathologic findings were those of mesangiocapillary glomerulonephritis, but considerable variability was observed. Lesions resembling diabetic glomerulosclerosis and amyloidosis were seen in some patients. Immunofluorescence findings in seven patients showed concomitant, equally intense staining for kappa light chain and immunoglobulin heavy chain (IgG or IgA), indicative of monoclonal immunoglobulin deposition. Specimens in the remaining cases stained predominantly for kappa light chain alone. In six cases the histologic and ultrastructural pattern was similar to that of type I mesangiocapillary glomerulonephritis. In three cases linear deposits were present, predominantly in subendothelial and inner glomerular basement membranes and, to a lesser degree, in mesangial locations, as in type II mesangiocapillary glomerulonephritis. In one of the latter cases dense deposits were intermixed with aggregates of amorphous fibrillar material indistinguishable from amyloid. In two cases involving IgA kappa chain deposition the histologic and ultrastructural appearance was that of mesangial glomerulonephritis. Considerable heterogeneity was found in the clinical features of the patient population. Specific clinical or serologic parameters for this disease could not be identified. Only one patient had an associated lymphoplasmacytic disorder. After follow-up periods ranging from six months to 17 years, all of the patients were alive, including four who had progressed to end-stage renal disease and required dialysis. Two of the latter patients underwent successful renal transplantation; one had been alive for five years and the other for three months without evidence of recurrence of the renal disease at the last follow-up examination.     

Psychophysiological reactions to noise as modified by personal control over noise intensity

Effects of personal control over noise intensity were studied in experimental situations where subjects performed mental arithmetic under noise exposure. Every other subject was offered a choice between noise intensities, and the next subject, serving as his yoked partner, had to submit to the same noise. Mean measures of catecholamine and cortisol excretion, and of heart rate and subjective effort and discomfort showed that subjects were more aroused in the yoked situation. There were, however, considerable interindividual differences, subjects classified as 'internals' or 'externals' on the basis of the Internal-External Locus of Control Scale responding to the two experimental conditions in congruence with their general beliefs and attitudes with regard to control.     

Initiation and direction of polymorphonuclear leucocyte locomotion. The particle collision hypothesis

A simple model of the initiation of locomotion, the random movement and the directional locomotion during chemotaxis is derived from observations on moving human polymorphonuclear leucocytes (PMNs). This model provides a unifying concept of initiation of PMN locomotion, PMN random movement and PMN chemotaxis. The lamellipodium is thought to be the direction-determining cell organelle.     

Life events and depression. Part 2. Results in diagnostic subgroups, and in relation to the recurrence of depression

Although there is evidence that the occurrence of stressful life events might be important for the onset and development of depression, it is still unclear whether differences occur in diagnostic subgroups of depressed patients, or in relation to type of episode, i.e., whether the first event or a relapse in a depression with a recurrent course. The present study has been carried out to investigate these issues more closely. Two hundred and six depressed patients have been classified into bipolar, unipolar, neurotic-reactive, and unspecified subgroups according to given definitions. The patients have also been classified into those suffering from a first episode and those suffering from recurrent depression. Each patient, when sufficiently improved, was given a semistructured interview, based on a specially constructed 56-item life events inventory. Unipolar and bipolar patients proved to have experienced significantly fewer events, even of the 'fateful' type (i.e., independent of depression) than the neurotic-reactive patients. However, this difference appeared to be due to difference in age among the groups and not to diagnosis. No difference occurred between uni- and bipolar patients. Patients with recurrent depression showed only small differences compared with patients in their first episode. These differences were consistently in the direction of fewer events in patients with recurrent depression. The implications of these results are discussed in relation to findings published by other authors.     

Lipomatous tumors: a correlative cytologic and histologic study of 27 tumors examined by fine needle aspiration cytology

A correlative cytologic and histologic study of 12 benign lipomatous tumors and 15 liposarcomas (well-differentiated, myxoid, round cell, and pleomorphic) is presented. In two cases the fine needle aspiration material was embedded in Epon for light and electron microscopic examination. Good correlation was found between the histologic and cytologic findings in the fine needle aspiration material. Pitfalls in the cytologic diagnosis of regressively changed lipoma, intramuscular lipoma, angiolipoma, hibernoma, and lipoblastoma, which may lead to an erroneous diagnosis of liposarcoma, are illustrated. The cytologic appearances of the liposarcomas varied with histologic type, although in all of these tumors the main criterion was the presence of atypical multivacuolated lipoblasts with characteristically scalloped nuclei. Staining of the aspirated material with Alcian blue at varying pH levels for characterization of the glycosaminoglycan content may help in the distinction of myxoid liposarcomas from myxoid chondromatous tumors and chordomas. May-Grünewald-Giemsa staining is considered the most useful staining method, while fat staining is considered of limited or no value in the cytologic diagnosis of lipomatous tumors. Epon embedding of fine needle aspirates for light and electron microscopic examination seems to be a useful diagnostic technique.