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Nucleotide variation at the ribosomal protein 49 (rp49) gene region has been studied in 75 lines of Drosophila subobscura belonging to four chromosomal arrangements (Ost, O3+4, O3+4+8, and O3+4+23). The location of the rp49 gene region within the inversion loop differs among heterokaryotypes: it is very close to one of the breakpoints in heterozygotes involving Ost chromosomes, while it is in a more central position in all other heterokaryotypes. The distribution of nucleotide polymorphism in the different arrangements is consistent with a monophyletic origin of the inversions. The data also provide evidence that gene conversion and possibly double crossover are involved in shuffling nucleotide variation among gene arrangements. The analyses reveal that the level of genetic exchange is higher when the region is located in a more central position of the inverted fragment than when it is close to the breakpoints. The pairwise difference distributions as well as the negative values of Tajima's and Fu and Li's statistics further support the hypothesis that nucleotide variation within chromosomal arrangements still reflects expansion after the origin of the inversions. Under the expansion model, we have estimated the time of origin of the studied inversions.

A region of approximately 1.6 kb encompassing the ribosomal protein 49 gene (rp49) has been sequenced and compared in nine species of the obscura group of Drosophila: four species belonging to the obscura subgroup, three to the pseudoobscura subgroup, and two to the affinis subgroup. Our data provide strong support that the nearctic species (pseudoobscura and affinis subgroups) are monophyletic and place D. bifasciata with the other species of the obscura subgroup. Nucleotide sequence information at the rp49 gene region (located very close to one of the breakpoints of inversion O3) has also been used to infer the phylogeny of the O chromosome in the subobscura species cluster. Analysis based both on parsimony-informative sites and on genetic distances confirms that the O3 gene arrangement, present in D. guanche (together with inversion g) and in D. madeirensis, is ancestral to gene arrangements O3 + 4 and Ost present in extant populations of D. subobscura.

Motivation: Several methods in molecular population genetics have recently been described to estimate the amount and pattern of the DNA polymorphism in natural populations, and also to test the neutral theory of molecular evolution. These methods are essential for understanding the molecular evolutionary process. However, a comprehensive computer program for the analysis is not currently available., Results: Here we present DnaSP (DNA Sequence Polymorphism) version 2.0, a software package for Windows that performs extensive population genetics analyses on DNA sequence data. DnaSP estimates several measures of DNA sequence variation within and between populations, linkage disequilibrium, recombination, gene flow and gene conversion (a new algorithm to detect gene conversion tracts has been included). DnaSP can also carry out several tests of neutrality: those of Fu and Li; Hudson, Kreitman and Aguadé; and Tajima. The results of the analyses are displayed in tabular and graphic form., Availability: For academic uses, DnaSP is available via anonymous ftp: ftp.ebi.ac.uk in the directory/pub/software/dos.

DNA sequence variation studies report the transfer of small segments of DNA among different sequences caused by gene conversion events. Here, we provide an algorithm to detect gene conversion tracts and a statistical model to estimate the number and the length distribution of conversion tracts for population DNA sequence data. Two length distributions are defined in the model: (1) that of the observed tract lengths and (2) that of the true tract lengths. If the latter follows a geometric distribution, the relationship between both distributions depends on two basic parameters: psi, which measures the probability of detecting a converted site, and phi, the parameter of the geometric distribution, from which the average true tract length, 1/(1-phi), can be estimated. Expressions are provided for estimating phi by the method of the moments and that of the maximum likelihood. The robustness of the model is examined by computer simulation. The present methods have been applied to the published rp49 sequences of Drosophila subobscura. Maximum likelihood estimate of phi for this data set is 0.9918, which represents an average conversion tract length of 122 bp. Only a small percentage of extant conversion events is detected.

DnaSP, DNA sequence polymorphism, is an interactive computer program for the analysis of DNA polymorphism from nucleotide sequence data. The program, addressed to molecular population geneticists, calculates several measures of DNA sequence variation within and between populations, linkage disequilibrium parameters and Tajima's D statistic. The program, which is written in Visual Basic v. 3.0 and runs on an IBM-compatible PC under Windows, can handle a large number of sequences of up to thousands of nucleotides each.

The brains of 200 patients who died with Acquired Immunodeficiency Syndrome (AIDS) from Berlin were examined retrospectively. This study was specifically intended to evaluate and document the prevalence of neuropathologic abnormalities, establishing the frequency of the various types of structural lesions, their combinations, their relative incidence, and the risk factors involved in different age groups. The data were compared and contrasted with the findings reported from other parts of the world and other German cities. It was found that the mean age of this group of patients was 41.4 years old, 75% were homosexual/bisexuals (H/B) and 18.5% were drug abusers (DA). Only 5.5% were women. Brain parenchymal changes, called in this report, HIV-related encephalopathy (HIVRE), characterized by vacuolization or spongy changes and astrocytosis in the subcortical white matter, and occasionally in gray matter, were found in 67 patients (33.5%). Drug abusers had a higher incidence of HIVRE (59.5%) compared with homosexual/bisexuals (28%). This is statistically significant (p < 0.0005). CMV encephalitis was found in 26 patients (13%) (8% of the drug abusers in contrast to 13% in the homosexual/bisexuals group). Primary central nervous system lymphoma (PCNSL) was seen in 28 patients (14%) regardless of the risk factor involved. 20 (13%) of the 150 H/B and 3 (8%) of the 37 DA had CMV encephalitis. Of the 150 H/B, 24 (16%) had PCNSL compared with only 4 of 37 (11%) of the DA. A significant incidence of opportunistic infections, both protozoal and viral was found in all groups. Cerebral toxoplasmosis occurred in 68 patients (34%). Microglial (phagocytic) nodules, probably related to CMV or cerebral Toxoplasmosis, were observed in 40 cases (20%). Diffuse microglial proliferation was noted in 104 patients (52%). Cerebral cryptococcosis was found in three patients. Progressive multifocal leukoencephalopathy was seen in 16 patients (8%). Various combinations of CNS pathological processes were found in 44 of the patients (22%). These include concomitant infections with Toxoplasma gondii and HIVRE in 13 patients; Toxoplasmosis and PCNSL in 8 patients; Toxoplasmosis with CMV and HIVRE in 4 patients; Toxoplasmosis with CMV in 2 patients; Toxoplasmosis with PCNSL and CMV in 2 patients; Toxoplasmosis with PCNSL and HIVRE in 2 patients and Toxoplasmosis with PML and HIVRE in 2 patients; Cerebral CMV with PCNSL and HIVRE in 4 patients; Cerebral CMV with HIVRE in 2 patients; PML with PCNSL in one patient; PML with HIVRE in 2 patients; and PML with PCNSL and HIVRE in one patient. Cerebrovascular lesions were found in 34 patients (17%).(ABSTRACT TRUNCATED AT 400 WORDS)

The DNA sequences of the ribosomal protein 49 (rp49) region were determined for 34 isochromosomal strains of Drosophila subobscura representing two chromosomal arrangements, the OST and the O3 + 4 gene arrangements, which differ by two overlapping inversions. The data reveal that gene conversion is a mechanism responsible for the transfer of genetic information between naturally occurring inversions of Drosophila. The estimated rate of gene transfer by gene conversion at this region, which is close to an inversion breakpoint, is lower than previous estimates obtained experimentally at the rosy (ry) gene in Drosophila melanogaster. Our data indicate that gene arrangements OST and O3 + 4 are monophyletic and rather old (0.58 and 0.73 million years old, respectively).

Introduction: Classical treatment of advanced heart failure is mainly based on the intravenous administration of inotropic drugs and vasodilators. Phosphodiesterase-III inhibitors, drugs whose effectiveness is not affected for the beta-receptor downgrading, may be particularly helpful in patients with severe heart failure refractory to conventional treatment with dopamine, dobutamine and/or nitroprusside., Patients and Methods: We have analysed the hemodynamic effects of milrinone in 13 patients (11 men, 2 women, mean age 55 +/- 12 years) with advanced heart failure resistant to dopamine, dobutamine and/or nitroprusside. Basally, before milrinone was administered, mean cardiac index and pulmonary capillary wedge pressure were 1.9 +/- 0.4 l/min/m2 and 25 +/- 6 mmHg, respectively. Milrinone was administered intravenously with a initial dose of 50 micrograms/kg over 10 minutes and followed by and infusion of 0.75 micrograms/kg/min over 6 hours., Results: During milrinone administration cardiac index and stroke volume index significantly increased (40% and 28%, respectively) (p < 0.05). Furthermore, systemic and pulmonary vascular resistance indexes significantly decreased (17% and 30%, respectively) (p < 0.05). Mean right atrial pressure and pulmonary capillary wedge pressure also decreased (36% and 20%, respectively), but differences did not reach statistical significance. Milrinone was well tolerated and no patient presented serious side-effects., Conclusion: Our results suggest that in patients with advanced heart failure refractory to conventional treatment with dopamine, dobutamine and/or nitroprusside, the addition of milrinone significantly improves parameters of systolic function.

Two cases of patients with unusual pleomorphic tumors in the meninges are reported. Histologically and immunohistologically, the tumor cells may be histiocytic in appearance. Computed tomography and magnetic resonance imaging scans, however, revealed no lesions in the parenchyma or in the meninges. The cytological examination of the cerebrospinal fluid revealed only a light lymphocytic reaction without tumor cells in both cases and thus led to misinterpretations as meningoencephalitis. One patient presented psychiatric symptoms. Related clinical problems and the possible histogenesis of the tumors are discussed.

Nucleotide variation in the region including the ribosomal protein 49 (rp49) gene was investigated by direct sequencing of 10 alleles of Drosophila subobscura from chromosomes differing in gene arrangements. Fifty-six nucleotide and seven length polymorphisms were detected over a 1.5-kb region. Of the 20 nucleotide polymorphisms present more than once in the sample, 13 were segregating in O[3 + 4], 9 in O[3 + 4 + 8], and 4 in O[st] chromosomal classes. Several of these polymorphisms were segregating in more than one chromosomal class, a strong indication of genetic transfer between different chromosomal gene arrangements either by double crossover or gene conversion. Given the probable role played by gene conversion in the history of the rp49 region in D. subobscura, estimates of nucleotide diversity within chromosomal class indicate that the O[3 + 4] chromosomal gene arrangement is older than the O[st] arrangement.

Mitochondrial DNA, sex linked allozymes, and chromosome A gene arrangement data, from eight European natural populations of Drosophila subobscura, were analyzed to determine the existence of latitudinal clines. Strong north-south correlations with latitude were found for gene arrangements and for the Hbdh and 6Pgdh allozymes. Gametic associations between the A2 gene arrangement, the Hbdh96 and the 6Pgdh96 alleles, point out some kind of epistatic interaction. At mtDNA level, the Hae III, A variant did not show a previously found north-south clinal variation.

A 14-month-old girl had three epileptiform attacks in the course of 6 months, each consisting of rhythmic movements of the right arm and right hand of 5 minutes' duration, followed by a 15-minute period of weakness. There were otherwise no abnormal neurological signs. Prenatal and perinatal development had been uneventful and the mother was healthy. Computed tomography showed a tumour in the left frontoparietal region. Surgery revealed an intracerebral tumour 7 cm in diameter with two large cysts; it was not sharply demarcated from the brain parenchyma, had no connection with the dura and was not infiltrating the ventricular system. The tumour was completely removed and at follow-up 18 months later there was no evidence of recurrence. Histological and immunohistochemical investigations showed that the tumour consisted of closely interwoven astrocytes and fibroblasts, two different cell types the latter of which does not normally occur in the brain. Exact immunohistochemical analysis of the components of a tumour is important because, unlike pure glial tumours, gliofibromas have a good prognosis after complete resections.

Background: To describe the clinical features and prognosis of the patients with cardiac tamponade admitted in the coronary care unit., Methods: Analysis the clinical data, etiology, treatment, and short term outcome of fifty three patients presenting with cardiac tamponade that required pericardiocentesis., Results: Neoplasm (21 cases) and idiopathic pericarditis (10 cases) were the most frequent causes of cardiac tamponade. In forty four patients an haemorrhagic fluid was obtained. Neoplastic pericardial fluid showed a higher haematocrit than the rest (18 +/- 8% vs 7 +/- 5%, p less than 0.01). Recurrence of tamponade occurred in all but one neoplastic patients, and was early (less than 48 h) in 18 patients. Twenty seven patients underwent pericardiectomy, and recurrence was the most frequent indication (18 cases). Overall in-hospital mortality was 26%. Ten out of 14 deaths occurred in neoplastic patients and 2 deaths after myocardial perforation related to temporary pacemaker. No patient with idiopathic or post-pericardiotomy cardiac tamponade died., Conclusions: Short term outcome and prognosis in patients with cardiac tamponade mainly depends on the etiology. A high rate of early recurrence and death characterize the malignant cardiac tamponades.

To evaluate the hypothalamus as a possible site of metabolic modulation of GH secretion, we studied the GH response to insulin hypoglycemia (IHG) and nicotinic acid (NA)-induced FFA depression in the absence and presence of third ventricular (ivt) infusions of glucose, oleic acid (Ol-Ac), or beta-hydroxybutyrate (beta OHB). Four rhesus monkeys had been prepared for chronic remote iv and ivt infusions as well as blood sampling from the adjacent room. Statistical evaluation used a two-way analysis of variance and individual comparisons with Tukey's Studentized range test. The GH response (area under the curve +/- SE) to IHG was significantly reduced by a concomitant ivt glucose infusion (control, 1.0 +/- 0.1; IHG, 12.1 +/- 3.3; IHG plus ivt glucose, 7.0 +/- 1.2 microgram/L.120 min). The GH response to FFA depression was significantly reduced by ivt Ol-Ac or beta OHB infusion (control, 6.0 +/- 1.0; NA, 51.5 +/- 4.1; Na plus Ol-Ac, 81.2 +/- 1.3; NA plus beta OHB, 38.6 +/- 3.5 microgram/L.300 min). Introcerebroventricular infusions of glucose, Ol-Ac, or beta OHB alone had no effect on plasma GH, glucose, FFA, or beta OHB concentrations. These results provide evidence for a hypothalamic site of metabolic modulation of GH secretion in the rhesus monkey. This does not exclude an additional effect directly at the pituitary gland.

The hemodynamic response to amrinone was analyzed in 19 patients with severe heart failure (NYHA III or IV). In 17 patients, 2 bolus of amrinone (0.75 mg/kg) were administered with an interval of 30 minutes, while a single bolus only was administered in 2 patients. In all patients the initial bolus was followed by continuous perfusion of Amrinone (10 micrograms/kg/min in 17 patients; 7 and 5 micrograms/kg/min in the remaining two). Cardiac index increased from 1.8 +/- 0.2 to 2.5 +/- 0.4 l/min/m2 (p less than 0.01), and pulmonary capillary wedge pressure and mean right atrial pressure decreased significantly (from 24 +/- 5.2 to 14 +/- 6 mmHg, p less than 0.01; and from 8.7 +/- 6.5 to 3.2 +/- 3.4, p less than 0.05 respectively). There were no significant changes in mean blood pressure (93 +/- 17 versus 88 +/- 13), heart rate (81 +/- 15 versus 84 +/- 14 beats per minute) and systolic work index (26.4 +/- 10.7 versus 37.7 +/- 12.3 g-m/m2). The maximum effect was obtained at 60 minutes and maintained throughout the period of monitoring (8 hours). In the 2 patients who received a single bolus of amrinone the maximum effect was reached at 30 minutes (cardiac index 1.3 +/- 0.1 versus 2.5 +/- 0.1 l/min/m2; pulmonary capillary pressure 24 +/- 5 versus 16.8 +/- 6.5 mmHg; mean right atrial pressure 11 +/- 1 versus 3.5 +/- 3.5 mmHg), and was followed by a progressive loss of efficiency, until effect had totally disappeared and situation basal returned, between the third and fourth hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuropathological findings from 8 individual cases of cerebral lymphomas in AIDS patients with consideration of the clinical, radiological, immunopathological, and other pertinent data selected from a series of 80 patients between 1985 and 1989 were studied. A wide variation in pathology was noted among our cases. It has been shown that lymphoma as a neuropathological diagnosis can coexist with a wide range of other characteristics, including toxoplasmosis, glial nodules, neuronophagia, degeneration, bleeding, hypoxia, progressive multifocal leucoencephalopathy, and myelopathy, although none of these attributes appeared more than casually interrelated. In general, the late-stage manifestations of lymphoma as were observed in this study, tended to be poorly localized, often simultaneously meningeal, perivascular, and diffuse in character. An important distinction between cerebral lymphomas of AIDS and non-AIDS patients is the highly atypical, clinically unreliable computer tomographic signals observed in several of our cases. Five of the six immunopathological investigations showed a preponderance of B-cell markers, corresponding in toto to high-grade non-Hodgkin lymphoma. One case exhibited immunohistological markers typical of Hodgkin's lymphoma (antibody CD-30). Of 6 obtainable serum specimens from our 8 cases, 4 showed high (greater than 2000) IgG titers against the EBNA-1 antigen of Epstein-Barr virus (EBV), of these three had IgM titers further supporting viral reactivation. One showed a normal IgG titer, yet with a significantly raised IgM titer.

We studied class II antigen expression and tumor-infiltrating leukocytes (TIL) in tissue sections of 69 squamous cell carcinomas of the larynx and 24 lymph node metastases in the neck. HLA-DR expression was found only in eight well-differentiated, highly keratinizing squamous cell carcinomas comprising seven of the verrucous variety and one ventriculosaccular tumor. None of the metastases was positive for DR antigen. Neither primary tumors nor autologous metastases stained for DP or DQ antigens. DR-positive tumors shared a peculiar pattern of TIL composed mainly of T cells, most of which belonged to the cytotoxic/suppressor subset, and B cells. These neoplasms had in common a slow rate of growth, and are considered low-grade carcinomas in the literature. We conclude from our study that HLA-DR expression seems to characterize tumors with a prominent infiltrate and an excellent prognosis.

Computer tomographic and histopathological findings in 55 patients who died of the complications of acquired immunodeficiency syndrome, were reviewed retrospectively. In 23 patients (42%) an increased space of the internal or external cerebral spinal fluid was diagnosed. 20 patients (36%) had focal lesions. We differentiated between single, multiple and ring-shaped lesions with contrast enhancement and hypodense lesions. In 12 cases (22%) no CT abnormalities were found. Focal lesions proved to be secondary to toxoplasmosis in 85%. Single lesions were never caused by toxoplasmosis.

Twenty five gliomas (5 oligodendrogliomas, 8 oligoastrocytomas, 5 astrocytomas grades I-II, and 7 malignant astrocytomas-glioblastomas) were studied with the immunohistochemical technique avidin-biotin complex (ABC) for myelin basic protein (MBP). We found four patterns of positivity with variable degrees and frequencies in the different types of tumors. We believe this method can help in the diagnosis of non-characteristic gliomas, particularly oligoastrocytomas.

The usefulness of routine intrapericardial pressure determination and hemodynamic monitoring during therapeutic (n = 22) or diagnostic (n = 2) pericardiocentesis was analyzed. Hemodynamic data confirmed the presence of cardiac tamponade in all cases, including the 2 patients without clinical suspicion. Prior to fluid evacuation, abnormally elevated levels of intrapericardial (13 +/- 5 mmHg), right atrial (14 +/- 4 mmHg) and pulmonary capillary (16 +/- 3 mmHg) pressures were observed. A significant correlation was found between intrapericardial and right atrial pressures (r = 0.97, p less than 0.05) and also between intrapericardial and pulmonary capillary pressures (r = 0.69, p less than 0.05). The basal cardiac output was low (3 +/- 1 l/min) and increased after the pericardiocentesis in all but one patient. According to the results of pericardiocentesis, patients were classified into three groups. Group I: intrapericardial and right atrial pressures decreased to normal levels. The increment of cardiac output was high (72%) and the procedure was considered successful. Group II: right atrial and intrapericardial pressures remained elevated (7.7 +/- 4 and 7 +/- 2 mmHg, respectively) and the cardiac output increment was less marked (52%), thus indicating incomplete drainage. Group III: intrapericardial pressure decreased to normal levels but right atrial pressure remained elevated. All these patients were found to have associated cardiac disease, most frequently constriction. We conclude that routine determination of intrapericardial pressure: 1) reveals the presence of tamponade in cases without clinical suspicion; 2) indicates the efficacy of drainage; and 3) together with right atrial pressure recording, provides early diagnosis of associated cardiac disease, especially effusive-constrictive pericarditis.

This case represents an example of clinically occult, disseminated neoplastic disease with almost asymptomatic but severe involvement of the central nervous system. The only helpful diagnostic investigation appeared to be cerebrospinal fluid cytology. Extensive post mortem examination was inconclusive as to whether the widespread CNS involvement with melanoma was primary or secondary.

In human and cat meninges the presence of adrenergic neurons was studied. The human meninges were obtained from 10 adult individuals 1-3 hours postmortem and the 6 cats meninges, one pretreated 7 days before the experiment with 5 mg of 6-OHDopamine intracisternally. In human and cat meninges, adrenergic granulations, located in fibers that form a reticulum around the arterial, arteriolar and small vein vessels were observed. These adrenergic fibers appeared forming a very dense reticulum in the adventitia of the small calibre arteries and in arterioles. In addition, in some vascular sectors, a considerable number of triangular or elongated cells, whose cytoplasm is full of adrenergic granulations can be observed isolated or in close vicinity to the adrenergic reticulum. In the meninges of the cat treated with 6-OH-Dopamine there was no adrenergic granulation. Furthermore, the radioenzymatic determination of noradrenaline content in 3 human meninges shows the existence of this amine. The number of cellular elements with adrenergic granulations is notable and permits one to suspect that this cellular system can play an important role in the autoregulation on the cerebral circulation together with the perivascular adrenergic reticulum.

The fine structural features of microcirculation in benign gliomas, as compared to those in glioblastomas have insufficiently been studied. 36 astrocytomas and oligoastrocytomas (grades I and II) were examined with the electron microscope in order to classify the arterioles, capillaries and venules of these tumours. In all the gliomas, the number of arterioles was smaller than in the normal brain parenchyma. A thickening of the subendothelial basement membrane could be assessed regularly. In the architecture of the small vessels numerous transitional forms could be found in many cases. On this basis the designation "capillary-like" and "venule-like" vessels seems to be justified. As a rule, the venule-like vessels are more numerous than the capillaries. The pericapillary and particularly the perivenular spaces are frequently dilated. In a few areas no continuous perivascular sheath of astrocytic foot processes are formed. At places glial processes can be found in the perivascular spaces which are not covered by a basement membrane. Lack of arterioles can lead to disturbances in autoregulation, and the frequently pathological structure of the capillaries and venules can result in disordered transport of water and ions with consecutive oedema.

Hemorrhagic infarction of the basal ganglia was observed in 2 young adult patients with acute leukemia who presented with progressive hemiparesis combined with severe mental alterations. In case 1 (AML) lethal infarction due to thrombosis of both internal cerebral veins occurred during induction therapy for relapsed leukemia; in case 2 (cALL) a devastating stroke probably due to deep cerebral venous thrombosis happened during the third remission. Neither of them had hyperleukocytosis, signs of infection, disseminated intravascular coagulation or CNS leukemia. We discuss long-term glucocorticoid therapy (case 1) and combined prophylactic CNS treatment (case 2) as possible risk factors for cerebrovascular thrombosis in acute leukemia.