Cranial anatomy of oreopithecus.

Reexamination of the 1958 skull of the late Miocene Oreopithecus bambolii revealed a cranial anatomy different from that widely accepted for this taxon. There is a sagittal crest, a high nuchal crest, a large gonial angle, and alpha high, rather vertical, occiput. This catarrhine was not a very large brained primate compared to known advanced hominoids.

Kinetic study of zinc sulphate release from lipophilic matrices prepared for the therapy of Wilson's disease.

The rate and extent of drug release from the most controlled release wax matrices are influenced by the drug loading/embedding excipient ratio of the systems. In the present study hydrophobic wax - zinc sulphate matrices with different drug loadings were prepared for the therapy of Wilson's disease. The drug release was tested by the paddle method of USP and the dissolution data were analysed. Both the dissolution rate and kinetic profile can be controlled by alteration in the quantity of embedding material. Matrices of 75% zinc sulphate loadings showed steady state diffusion-controlled matrix release with good correlation in vitro. Good absorption of zinc sulphate from the gastrointestinal tract was proven by significant elevation of serum zinc level in patients with Wilson's disease.

Seasonal fluctuations of glial fibrillary acidic protein (GFAP) immunoreactivity in the rat suprachiasmatic nucleus.

The pacemaker of the "biological clock", the suprachiasmatic nucleus (SCN) of the hypothalamus was studied in intact male rats for glial fibrillary acidic protein (GFAP) a specific marker for astrocytes. Immunohistochemical reactions were carried out in winter (January-February) and in summer (June-July). In winter the GFAP-immunoreactivity of the SCN was found low whereas in summer it was high. Gonadectomy reduced differences. Since photic stimuli that apparently trigger the observed differences reach the SCN through identified neuronal pathways we conluded that the reaction of astrocytes is an indicator of seasonally altered neuronal function in the SCN.

Fasting-induced changes of neuropeptide immunoreactivity in the lateral septum of male rats.

The objective of the present study was to determine the rostrocaudal distribution and the effect of reduced food intake (60% of the average daily food intake for 1-4 weeks) on the amount of leucine-enkephalin (Leu-enk), neuropeptide Y (NPY) and galanin (Gal) in the lateral septum of male rat brain. Using pre-embedding immunocytochemistry combined with densitometry on 60 microm serial vibratome sections we found that in control animals Leu-enk-immunoreactive elements showed an increasing density from rostral towards the medial part of the septum, then a gradual decrease towards the caudal direction. The distribution of NPY proved to be rather even along the examined sequence of sections with two smaller peaks roughly at the 1/3 and 2/3 of the rostrocaudal axis. Gal showed similar distribution but the peaks were shifted to more caudal direction. We also found that Leu-enk forms the most dense plexus followed by a moderate amount of NPY-positive axonal meshwork. Gal was present in the lowest amount along the lateral septal nuclei. The effect of reduced food intake was marked and differential in the case of the three examined peptides. During the first 2 weeks of reduced food intake NPY-immunoreactivity was upregulated as compared to the control, then it was reduced close to the control value by the 4th week. The changes in Gal immunoreactivity showed similar pattern. The average relative density of Leu-enk-immunoreactive elements immediately decreased as a result of reduced food intake for 1 week and it gradually decreased by the end of the 4th week. These results indicate that reduced food intake affects the expression of NPY, Gal and Leu-enk not only in the relevant hypothalamic neuroendocrine centres, but also in the lateral septal area.

Decreased bone density, elevated serum osteoprotegerin, and beta-cross-laps in Wilson disease.

Osteopathia has been reported in Wilson disease (WD), but bone density has not been measured; therefore, we performed bone mineral density (BMD), bone mineral content (BMC), and quantitative bone ultrasound (QUS) assessments, as well as measured the serum levels of osteocalcin (OCN), beta-cross-laps (beta-CTx's), and the recently discovered osteoprotegerin (OPG) and its ligand RANKL to investigate the underlying mechanism of osseous disorders. Serum OCN, beta-CTx, OPG, and RANKL levels were measured by ELISA in 21 WD patients and in 20 age- and gender-matched healthy subjects. BMD, BMC, and QUS parameters were also determined. Osteoporosis was present in 9/21 (43%) WD patients. Abnormal QUS parameters were found in 7 (33%) of the patients. Although serum OCN levels were similar in patients and controls (29.93 +/- 24.65 mg/ml vs. 29.84 +/- 6.89 mg/ml), beta-CTx and OPG levels were significantly increased in WD compared with the healthy controls (625.4 +/- 312.3 pg/ml vs. 423.6 +/- 144.3 pg/ml and p = 0.022 and 7.2 +/- 3.4 pM vs. 3.5 +/- 1.0 pM and p < 0.001, respectively). No difference was observed in the RANKL level. There was a positive correlation between OCN and beta-CTx (r = 0.55; p = 0.01). We proved high occurrence of osteoporosis in WD. Negative bone remodeling balance is a consequence of increased bone resorption, which is indicated by elevated beta-CTx. The novel finding of elevated serum OPG may reflect a compensatory reaction to enhanced osteoclast activity, despite the normal OCN level.

Bone marrow transplantation in accelerated chronic granulocytic leukaemia using dibromomannitol-preconditioning instead of total-body irradiation.

In a preliminary study on five patients with accelerated CGL, transplantation of allogeneic matched bone marrow was shown to be feasible without whole-body irradiation. Animal experiments and studies with cells cultured in vitro suggest that the cytocastic drug used to kill leukaemic clones (Myelobromol-Chinoin) does not injure haemopoietic stroma. The administration of this protocol is cheap and easy. Our preconditioning does not, in itself, eradicate the malignant CGL clone immediately: 15-20% of marrow mitoses were Ph1+ one month after transplantation. For this reason, additional cytostatic therapy was given in the course of the 3rd to 6th post-transplant months. No Ph1+ cells were observed from the fourth post-transplant month onwards. Very few severe acute complications were seen and two out of three matched transplanted patients are disease-free 27 + and 13 + months later. On the basis of the developing normal spleen architecture and the changing pattern of circulating NAP score values, particularly the months-long persistence of distinctly low scores, and then the delayed emergence of normal levels, we put forward a hypothesis, emphasizing the role of environmental factors, including the formation of a normal haemopoietic stroma in the successfully transplanted CGL patient.

Immunologic and molecular biologic characterization of pleural involvement in a case of T-chronic lymphocytic leukemia.

Pleural involvement is a rare complication of chronic lymphocytic leukemia (CLL). We report a CLL case of T-cell origin (documented by cell surface marker as well as DNA rearrangement studies) where the lymphoid cells of the pleural fluid were found to belong to the same monoclonal population of T cells as those of the peripheral blood.

Expression of decorin, transforming growth factor-beta 1, tissue inhibitor metalloproteinase 1 and 2, and type IV collagenases in chronic hepatitis.

Decorin is a small extracellular matrix proteoglycan. It binds and modulates transforming growth factor (TGF)-beta 1 action, the major stimulator of fibrogenesis. Its role in the pathogenesis of human liver cirrhosis is unknown. Therefore, we studied the relationship of the 2 proteins in normal human liver and in 43 chronic hepatitis and liver cirrhosis specimens. To understand the mechanism that maintains matrix deposition in stage IV hepatitis, we studied expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, as well as the activities of type IV collagenases. Gene expression was analyzed on messenger RNA and protein level by morphologic and biochemical approaches. Decorin proved to be an early marker of fibrogenesis, and its deposition increased parallel to that of TGF-beta 1 and to inflammatory activity. Liver fibrosis progressed despite high temporospatial expression of decorin with TGF-beta 1. Neither decorin nor TGF-beta 1 protein deposition increased further in cirrhosis with low inflammatory activity, suggesting that impaired extracellular matrix catabolism rather than active production plays a role in this stage. This possibility was supported by high message levels of metalloproteinase inhibitors, no 72-kd collagenase activities, and low 92-kd collagenase activities.

Glial fibrillary acidic protein (GFAP)-immunoreactivity is reduced by castration in the interpeduncular nucleus of male rats.

The interpeduncular nucleus of adult male rats was investigated for glial fibrillary acidic protein immunoreactivity. In intact animals the nucleus had an outstandingly intense immunostaining, particularly at its periphery, including the rostral, lateral, dorsomedial and dorsolateral subnuclei where, in addition to neuropil astrocytes, a substantial amount of perivascualr glia was found. Four weeks after castration, immunostaining decreased markedly in the core region of the nucleus corresponding to the caudal and medial subnuclei, and to a much lesser extent at the periphery. The immunoreactivity in pericapillary astrocytes proved to be insensitive to castration. Testosterone, if administered after castration prevented or restituted the loss of immunoreactivity. Beyond 4 months after castration, the effect of testosterone gradually declined. It is concluded that testosterone stimulates the expression of glial fibrillary acidic protein immunoreactivity in the interpeduncular nucleus. Our findings support the argument that gonadal steroids can influence astrocytes also in non-endocrine areas of the brain.

Treatment of primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a presumed autoimmune disease of the liver, which predominantly affects middle age women. Most patients are diagnosed when asymptomatic. The disease is characterised by chronic, granulomatous inflammation of the small bile ducts, which leads to progressive ductopenia, cholestasis, fibrosis, cirrhosis and eventual liver failure. All PBC patients with abnormal liver biochemistry should be considered for therapy. Ursodeoxycholic acid (URSO) treatment reduces intracellular hydrophobic bile acid levels and thereby may have a cytoprotective effect on cell membranes. URSO may also act as an immunomodulating agent. Multicenter randomised controlled trials proved that the treatment is associated with a marked improvement in serum biochemical markers of cholestasis, i.e. bilirubin, ALP, GGT, including fall in serum cholesterol levels. Treatment does not seem to benefit the symptoms of fatigue, pruritus, and osteoporosis. UDCA has been shown when given in a dose of 15 mg/kg daily for up to 4 years to prolong the time to liver transplantation or death. Immunosuppressive therapy: based on the immunological abnormalities, several immunosuppressive drugs have been tested. Neither azathioprine nor cyclosporine was found in large enough trials to show beneficial effect on survival. D-penicillamine, cholchicin, methotrexát, prednisolone were found without significant long-term benefit. Combination therapy with URSO and budenoside appears to add some benefit to URSO monotherapy, but further studies are needed. Liver transplantation. The most crucial question is the timing. Serum bilirubin, Mayo risk score and some other factors such as uncontrollable pruritus and severe osteoporosis influence the decision. Recurrence of PBC in allograft is rare, the progress is slow, and is no reason for not recommending transplantation. Symptomatic treatment of pruritus, sicca syndrome and preventive treatment of osteoporosis, neuropathy and fat soluble vitamin deficiency is also important.

Ovarian cycle-related changes of glial fibrillary acidic protein (GFAP) immunoreactivity in the rat interpeduncular nucleus.

The interpeduncular nucleus (IPN) of female rats was studied across the estrous cycle to observe whether the expression of the astroglial marker, glial fibrillary acidic protein (GFAP) reacts to hormonal changes in an area not belonging to the 'endocrine brain'. A marked reduction of immunoreactive GFAP was observed in estrus as compared to the immunoreactivities in met- and proestrus. This finding is consistent with earlier observations in the endocrine hypothalamus, but also proves that gonadal steroids influence astroglia in brain regions not involved in neuroendocrine regulation. Since cyclic fluctuations of synaptic numbers in the female have been described only for the endocrine hypothalamus, decrease of immunoreactive GFAP in the IPN during estrus may reflect a down-regulation of GFAP synthesis.

Lipoprotein(a) concentration and phenotypes in primary biliary cirrhosis.

We studied a selected group of 39 female patients suffering from primary biliary cirrhosis (PBC). This disease is characterized by typical lipoprotein alterations and elevated concentrations of serum cholesterol. Despite the increased concentration of atherogenic lipoproteins, enhanced atherogenesis is not characteristic of PBC. Serum total cholesterol, triglycerides, HDL2 and HDL3-cholesterol concentrations were measured by enzymatic methods or in combination with precipitation procedures. Apolipoproteins were determined by using immunonephelometric methods. ELISA sandwich method was used for lipoprotein(a) determinations. Apoprotein(a) phenotyping (isoforms) was performed by Western blotting with specific antibodies. The concentrations of serum lipids, lipoproteins and apoproteins (AI, AII and B) were found in the range of earlier investigations. The serum lipoprotein(a) concentration did not differ between the PBC patients and control subjects (10.0/0.1-54/, median 2.55 vs. 11.5/0-75/, median 5.2 mg/dl). In the advanced stages of PBC we found a higher number of patients with low lipoprotein concentration (lower than 1 mg/dl). In patients with shorter durations and milder histological alterations high HDL2 cholesterol subfractions has been detected (stage I = 0.42 +/- 0.18, stage II = 0.53 +/- 0.29 and stage III = 0.62 +/- 0.41 vs. stage IV = 0.26 +/- 0.15 mmol/l, P < 0.05). Despite the elevation of atherogenic lipoproteins, high HDL2-cholesterol and normal lipoprotein(a) concentrations may be one of the reasons why patients with advanced PBC are not placed at increased risk for atherosclerosis.

Hepatocyte proliferation and cell cycle phase fractions in chronic viral hepatitis C by image analysis method.

OBJECTIVE: Chronic hepatitis is characterized by necrosis of liver cells, accompanied by an inflammatory reaction and compensatory cell proliferation. The interaction of the core and non-structural proteins of hepatitis C virus (HCV) with several cellular factors suggests that cell proliferation may be influenced by HCV. The aim of this study was to investigate hepatocyte proliferation and DNA ploidy patterns in patients with chronic viral hepatitis C (CH-C) compared with chronic non-viral hepatitis (CH-N), using a TV image analysis method. METHODS: The DNA index (DI) and cell phase fractions (G1, S, G2) were measured by means of digital picture analysis method on nuclear suspensions of Feulgen stained hepatocytes. Cells were taken from the liver biopsy specimens of 71 patients with CH-C and 24 patients with CH-N. Twenty-six normal liver samples were used as controls. RESULTS: Significantly higher G1 (94 +/- 4) and lower S (3.56 +/- 3.16) phase fractions were measured in CH-C compared with CH-N (G1, 90 +/- 6; S, 6.4 +/- 5.99). The DI of moderate (1.12 +/- 0.05) and severe (1.12 +/- 0.05) CH-C showed near-aneuploid DNA content, while diploidy (DI < 1.10) was detected in cases of CH-N. CONCLUSION: The higher G1 and lower S cell cycle phase fractions in CH-C reflect decreased hepatocyte proliferation compared with CH-N. The near-aneuploid DNA content of the HCV-infected liver samples may be a sign of increased genetic instability, which may contribute to the carcinogenic potential of HCV.

Retarded myelination in the lumbar spinal cord of piglets born with spread-leg syndrome.

Piglets born with spread-leg syndrome, a congenital weakness of the hindlimb adductors, were investigated to determine the site of lesion leading to limb impairment. Histological and immunohistochemical studies of the motor neuron unit showed no alterations but quantitative analysis revealed a reduction of axonal diameter and myelin sheath-thickness of the fibres innervating the adductors of the affected limbs. In the lumbar spinal cord a lack of myelination was observed in the tracts descending to the lower motor neurons. Recovery from the syndrome was accompanied by a catching-up of myelination with that of the controls. The spread-leg syndrome is due to a nutritional deficiency in the sow; thus it is assumed that the deficient maternal substances, mainly choline and methionine, are essential for the normal myelin production by spinal white matter oligodendrocytes of the fetus.

Where is mosquito research published?

To identify the core journals that publish articles on mosquito research, the Agricola database (covering 1985-89 citations) was analyzed. This source contained 3,007 citations to mosquito research, and the citations were found in 404 different serials. Whereas 10 serials (2.5% of total serials) in Agricola produced 50% of the citations, almost one-half of the serials in this source contained only one citation to mosquito research. Fifteen journals (the core journals) contained greater than 1% of total citations. The number of citations found among 126 different databases and abstracting services that were examined varied: 39 had no citations to mosquitoes, but 13 (including life-sciences, medical and even popular-literature databases) had greater than 100 citations. The choice of core journals will be an increasingly important decision by biological libraries as costs for journal subscriptions rise.

Comparison of VHS video recording system with apple Macintosh-based image analysis and modified CODA-3 systems in equine motion analysis.

A VHS video--computer-based image analysis combination is described as a low sampling rate motion analysis system. Video recordings were taken indoor without any artificial illumination at 25 fps sampling rate. The horse studied was running on a high-speed treadmill and observed at 1.6, 4 and 7 m/s velocities at walk, trot and canter, respectively. Left forelimb and hindlimb were recorded separately from lateral view. For comparison, parallel CODA-3 recordings were taken at the same time from the same position. Joint angles were expressed and compared in angle-time diagrams. Sampling of both systems has been synchronised by a timer device at +/- 1/300 s error level. Results obtained with the two different recording systems were comparable in all joints measured with the exception of the fetlock. Inaccuracies in fetlock recordings are thought to be eliminated by measuring at controlled illumination. As a conclusion, the VHS-Macintosh setup appears to be promising as a simplified system for gait analysis.

Sexual dimorphism of glial fibrillary acidic protein (GFAP) immunoreactivity in the rat interpeduncular nucleus.

The intensity of immunostaining for the glial fibrillary acidic protein (GFAP) is outstandingly high in the interpeduncular nucleus. This nucleus was compared in males and females for its GFAP immunoreaction. Immunohistochemistry was carried out on free floating vibratome slices and evaluated by surface densitometry. While in males the reactions were similar, females showed individual variations. Since the interpeduncular nucleus is a hormonally inactive brain area where gonadal hormones do not induce plastic synaptic changes, it is concluded that concerning this astroglial marker a sexual dimorphism exists also outside the "endocrine brain".

[Dry eye syndrome in patients with biliary cirrhosis]. / Száraz szem syndroma primer biliaris cirrhosisos betegekben.

Ophthalmic state of 18 women patients between 40 and 69 years of age with primary biliary cirrhosis (PBC) was studied. Tear secretion was studied by Schirmer I., break up time and conjunctival and corneal bengal rose staining tests. In 15 cases serious degree of keratoconjunctivitis sicca has been revealed. Xanthelasma of the lid was found in three patients. Visual functions were intact. Kayser-Fleischer ring was absent in every case. There was no connection between the duration or laboratory characteristics of the PBC and the severity of the keratoconjunctivitis sicca. In nine patients of the cases requiring tear substitution eye drops of methylcellulosum available in Hungary were insufficient. Hydroxypropyl-methylcellulosum drops of eye gel containing peptides of low molecular weight eliminated the symptoms in these cases. The authors emphasize that PBC should be considered as a possible underlying disease in women over 30 years with severe dry eye syndrome.

[Detection of antimitochondrial antibodies by immunodiffusion, ELISA and immunofluorescence methods]. / Antimitochondriális antitestek kimutatása immundiffúzios, ELISA és immunofluoreszcenciás módszerekkel.

Ouchterlony immunodiffusion and ELISA were used for the detection of antimitochondrial antibodies. The results were compared with those of immunofluorescence measurements. The occurrence of antimitochondrial antibodies was investigated in 20 patients with primary biliary cirrhosis, in 30 with autoimmune disease and in 28 with porphyria cutanea tarda. Sonicated rat liver mitochondria fractions were used as antigens. Among the patients with primary biliary cirrhosis, Ouchterlony immunodiffusion revealed antimitochondrial antibodies in 18 cases, whereas antibodies were not found in the other groups of patients, except for 1 case of systemic lupus erythematodes. ELISA demonstrated that in all 20 patients with primary biliary cirrhosis where immunofluorescence revealed antimitochondrial antibodies, there was an increase in the quantity of antibodies against mitochondrial inner membrane fractions, and in 7 cases even against the outer membrane fractions. These 7 were the most serious cases clinically. These methods allow the differentiation of antimitochondrial antibody subtypes and promote the establishment of the diagnosis.

[Interferon (Egiferon) therapy of chronic active hepatitis]. / Krónikus aktív B hepatitis interferon (Egiferon) kezelése.

Human leukocyta interferon (Egiferon) has been administered in 10 cases having HBsAg positive chronic active hepatitis. The treatment was started with 3 x 3 MU week for one month and either with 2 x 3 MU week or 3 x 3 MU week for 2 subsequent months. HBsAg negativity was found in cases of 4 and histological improvement in cases of 3 patients. The treatment was ineffective in 3 cases.