Secretion of kallikrein and its role in vasodilatation in the submaxillary gland

1. The effects of parasympathetic (chorda) and sympathetic nerve stimulation on the concentration and output of kallikrein secreted in saliva from the cat's submaxillary gland were compared. Sympathetic stimulation always produced a much higher concentration (up to 500 times) and output (up to 390 times) of kallikrein than parasympathetic stimulation. In the dog, in which sympathetic nerve stimulation produces little or no secretion from the submaxillary gland, there was also a marked increase in the secretion of kallikrein when sympathetic was superimposed on parasympathetic secretion. This effect did not occur, however, in the rabbit's submaxillary gland.2. It was possible to deplete the cat's submaxillary gland of kallikrein, either by ligation of the duct for several days or by duct ligation and sympathetic nerve stimulation, so that it was undetectable either in the gland or in saliva after stimulation of the chorda. Such glands, nevertheless, responded to chorda stimulation with a normal atropine-resistant vasodilatation.3. There is a close parallelism between the rate of secretion of salvia and vasodilatation over a range of frequencies of chorda stimulation, but the output (and concentration) of kallikrein in saliva is distinctly different for the same frequencies of nerve stimulation.4. Our results are consistent with the view that vasodilator nerves exist in the parasympathetic nerves to the submaxillary gland. We suggest that they are cholinergic in nature despite the fact that chorda vasodilatation is resistant to atropine. It is further suggested that neither the kallikrein-kinin system nor adrenergic vasodilator nerve fibres play a significant role in chorda vasodilatation.     

Morphological detection and quantification of lipoprotein(a) deposition in atheromatous lesions of human aorta and coronary arteries

Summary Lipoprotein(a), as an atherogenic particle, represents an independent risk factor for coronary heart disease. In the present study the morphological distribution of apoprotein (a) and apoprotein B within the arterial wall is described. Apoprotein B, a constituent of very low-density lipoprotein, low-density lipoprotein and lipoprotein(a) has previously been demonstrated in atheromatous lesions. Lipoprotein(a) possesses an additional protein, designated apoprotein (a). Autopsy material (n=74) from the left coronary artery and from the thoracic aorta has been examined by means of immunohistochemistry and both apoprotein (a) and apoprotein B were detected, primarily associated with the extracellular matrix and accumulating in lesions in the arterial wall. The staining pattern for both antigens was almost always found to be congruent, suggesting that the detection of (a)-antigen has to be attributed at least in part to the presence of lipoprotein(a). It is concluded that both low-density lipoprotein and lipoprotein(a) have an important role in the pathogenesis of atherosclerosis.     

Optimization of 3-D hepatocyte culture by controlling the physical and chemical properties of the extra-cellular matrices

Hepatocytes are anchorage-dependent cells sensitive to microenvironment; the control of the physicochemical properties of the extra-cellular matrices may be useful to the maintenance of hepatocyte functions in vitro for various applications. In a microcapsule-based 3-D hepatocyte culture microenvironment, we could control the physical properties of the collagen nano-fibres by fine-tuning the complex-coacervation reaction between methylated collagen and terpolymer of hydroxylethyl methacrylate-methyl methacrylate-methylacrylic acid. The physical properties of the nano-fibres were quantitatively characterized using back-scattering confocal microscopy to help optimize the physical support for hepatocyte functions. We further enhanced the chemical properties of the collagen nano-fibres by incorporating galactose onto collagen, which can specifically interact with the asialoglycoprotein receptor on hepatocytes. By correlating a range of collagen nano-fibres of different physicochemical properties with hepatocyte functions, we have identified a specific combination of methylated and galactosylated collagen nano-fibres optimal for maintaining hepatocyte functions in vitro. A model of how the physical and chemical supports interplay to maintain hepatocyte functions is discussed.     

Prolongation of small bowel allograft survival with a sequential therapy consisting of a synthetic MHC class II peptide and temporarily low-dose cyclosporine A

It has been extensively documented the role of the indirect pathway of allorecognition in allograft rejection. However, recent data demonstrate that the manipulation of this pathway could be also sufficient to promote prolongation of allograft survival. In the present study we evaluated the effect of preoperative immunization with the WF-specific MHC class II peptides RT1.D2 and RT1.B2 in combination with low-dose CsA from days 0 to 7 (5 mg/kg/day) and from days 8 to 30 (1 mg/kg/day) after WF small bowel transplantation. Seven days before and on the day of transplantation, LEW recipients were immunized with the two WF MHC class II peptides RT1.B2 and RT1.D2. The CsA monotherapy induced an allograft survival of 49.3 +/- 6.1 days. MHC class II peptide immunization had a limited effect on allograft survival for RT1.D2 (47.1 +/- 3.8 days) and induced prolongation of allograft survival for RT1.B2 (73.6 +/- 34.6 days). This effect seems to be based on the absence or silence of RT1.B2-reactive T cells and rejection seems to be correlated with the presence of RT1.B2-specific T cells in the late phase. Therefore, the combination of RT1.B2 with low-dose CsA shifts the immunological response and protects small bowel allograft rejection.     

Enhanced MYCN expression and lsochromosome 17q in pineoblastoma cell lines

We have established two cell lines, PER-452 and PER-453, from an 8-month-old girl with an extensive pineoblastoma. Characterization of these lines revealed that the proto-oncogenes MYC and MYCN were not amplified, but both cell lines showed MYCN expression comparable to a cell line with 200-fold MYCN amplification. Both cell lines contained an i( 17q). These results support the concept that pineoblastomas belong to a larger group of primitive neuroectodermal tumors of the central nervous system. These two cell lines provide a unique opportunity to investigate the molecular genetic mechanisms underlying these neoplasms further. Genes Chrom Cancer 9:129-135 (1994).© 1994 Wiley-Liss, Inc.     

Alteration of the LRP1B gene region is associated with high grade of urothelial cancer

We have delineated regions of interest at chromosome 2q21.2, 2q36.3, and 2q37.1 by deletion mapping of 114 urothelial cancers (UC). Altogether, 17%, 18%, and 63% of the G1, G2, and G3 tumors displayed loss of heterozygosity at chromosome 2q, respectively, The region at 2q21.2 was narrowed down to the LRP1B gene (NT_005129.6). Hemi- and homozygous deletion at the LRP1B gene region was seen in 31 of 114 UCs. Only 8% of the UCs with G1 and none with G2 tumors showed loss of heterozygosity at the LRP1B gene, whereas 49% of the G3 UCs had allelic loss at this region. RT-PCR analysis of the LRP1B gene showed the lack of expression of several exons in 2 of 9 cases analyzed. Our analysis suggests that the LRP1B gene is a candidate tumor suppressor gene in UCs.     

Transmission of tuberculosis between men and pet birds: a case report

The present report describes a case of Mycobacterium tuberculosis infection in an African Grey parrot (Psittacus erithacus erithacus) kept as a pet bird. Diagnosis was confirmed by microbiologic and pathologic results, and indicated a human–avian transmission. Clinical signs included sublingual nodules resulting in anorexia and signs of osteolysis in the long bones. Proliferation consisted of several nodules with small greenish-caseous foci in cross-section and revealed a severe granulomatous inflammation without intralesional acid-fast rods. M. tuberculosis was cultured from a pooled sample of sublingual and liver nodules, and was confirmed via polymerase chain reaction. Transmission between men and parrot was proved by spoligotyping pattern analysis. The absence of facial skin lesions and acid-fast rods within the tubercles is contrary to previous publications of tuberculosis in birds. This disease in a common pet bird species is of zoonotic importance, and those parrots with close contact to owners suffering from tuberculosis may serve as a potential reservoir for human infection.     

Changes in cerebral endothelial barrier antigen, without alteration of permeability for intravenously injected leptin in diet-induced obesity in rats

Leptin, a potent anorectic, 16-kDa, adipose tissue-derived protein, predominantly acts in hypothalamic nuclei, signaling obesity and modulating ingestive behavior. To reach this brain area, leptin, probably has to cross the blood-brain barrier (BBB). In some cases of obesity, enhanced leptin levels in the blood do not result in anorectic effects, probably due to an altered leptin transport across the BBB. Therefore, we investigated the BBB in lean and diet-induced obese Lewis rats. To obtain information about the presence of microvessels with barrier dysfunction we examined three brain areas (hypothalamus, cortex, hippocampus) using a monoclonal antibody which detects intact microvessels of the BBB (anti-endothelial barrier antigen, anti-EBA). The results showed a significantly reduced EBA staining in the brain sections of the obese animals, except the hippocampus, compared to the control group. In a second step we injected I125-labeled leptin intravenously (i.v.) in permanent i.v.-cannulated, unrestrained Lewis rats (lean and obese). We measured the radioactivity in the cerebrospinal fluid after puncture of the cisterna magna, in the blood and brain tissue 90 min after injection. The leptin content in the cerebrospinal fluid and brain was not reduced in obese compared to lean rats, thus showing a similar transport capacity of the BBB in both experimental groups. Therefore, the results of the in vivo investigations do not indicate an impairment of the BBB in diet-induced obesity, despite the immunohistological findings. Further functional and morphological studies are necessary to evaluate the specific role of other organs and distinct forms of leptin (free and protein-bound) in the pathogenesis of diet-induced obesity.