Biomedical subjects
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Malignant lymphoma is rarely seen in the hand. We present a case of malignant lymphoma of the hand with Ga-67 citrate and MR images, and discuss the usefulness of Ga-67 citrate scintigraphy for diagnosing this condition.
Methionine adenosyltransferase (MAT) catalyzes the synthesis of S-adenosylmethionine (AdoMet) from ATP and L-methionine. AdoMet is the major methyl donor in most transmethylation reactions in vivo, and it is also the propylamino donor in the biosynthesis of polyamines. In the present study, we assessed MAT activity in human colons with colorectal carcinoma and the values were compared with those of morphologically normal adjacent mucosa. Higher levels of MAT activity were observed in the colorectal carcinoma than in the normal colon. The ratio of MAT activity in tumor tissue versus normal tissue seemed to be correlated well will the stage of the colorectal tumor. Furthermore, immunoblot analysis showed that the high levels of MAT activity observed in colorectal carcinoma were due to the increased amounts of MAT protein. Immunohistochemical analysis revealed that MAT was most abundant in goblet cells, particularly in granules in the supranuclear area of these cells. In the colorectal carcinoma tissues, MAT was strongly stained in the cancerous cells and localized in granules in the supranuclear region. The results of this preliminary study suggest that determination of the relative ratio of MAT activity in both normal and tumor regions in human colorectal carcinoma could be a clinically useful tool for determining the stage of malignancy of colorectal carcinomas.
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[reaction: see text] Replacement of the negatively charged phosphodiester linkages of RNA with positively charged guanidinium linkages provides the polycationic ribonucleic guanidine (RNG). RNG is anticipated to bind strongly to target DNA/RNA through the specific interactions of nucleobases and the attractive electrostatic interactions of backbones. Preparation of building blocks and the solid-phase synthesis of RNG are reported. Both trimeric and pentameric uridyl RNG have been synthesized.
The occurrence of N-linked oligosaccharides lacking galactose is significantly higher than normal in serum IgG of patients with rheumatoid arthritis (RA) in whom rheumatoid factor (RF), an autoantibody against autologous IgG, has been detected. In the present study, IgGs with and without RF activity (IgGRF and non-RF IgG, respectively) were prepared from sera of RA patients, and their oligosaccharide structures were characterized in order to investigate the relationship between RF activity and glycosylation. Three IgGRF fractions and a non-RF IgG fraction were obtained based on their ability to bind to an IgG-Sepharose column. The specific RF activity, as measured by immunoassays, was highest in the IgGRF fraction, which bound most avidly to the IgG-Sepharose. When the oligosaccharides were released by hydrazinolysis, and analyzed by MALDI-TOF mass spectrometry and HPLC, in combination with sequential exoglycosidase treatment, all the IgG samples were found to contain a series of biantennary complex-type oligosaccharides. The incidence of galactose-free oligosaccharides was significantly higher in both IgGRFs and non-RF IgG from RA patients compared with IgG from healthy individuals. In all IgGRFs, the levels of sialylation and galactosylation were lower than those in non-RF IgG from RA patients; the sialylation of non-RF IgG was the same as that of IgG from healthy individuals. In addition, the decreases in galactosylation and sialylation of oligosaccharides in IgGRF correlated well with the increase in RF activity. These findings could contribute to our understanding of the mechanisms of IgG-IgG complex formation and the pathogenicity of these complexes in RA patients.
Rheumatoid factors (RFs) are autoantibodies, which recognize antigens on a constant region of immunoglobulin G (IgG). Among various RF classes, RF of the IgG class (IgGRF) forms immune complexes in rheumatoid joints and is implicated in the pathogenesis of rheumatoid arthritis (RA). To characterize the formation of IgGRF immune complexes, in the present study, IgGRF was isolated from sera of RA patients, and its interaction with immobilized IgG was analyzed and compared to that of IgMRF or IgARF by means of surface plasmon resonance. On gel filtration, the IgGRF was eluted as a single peak corresponding to IgG, excluding the possible formation of self-associating IgGRF complexes in solution. Sensorgrams of the interaction of IgGRF with immobilized IgG revealed that it clearly bound to the IgG at 6 degrees C, but not at 30 degrees C. The degree of interaction decreased inversely with an increase in temperature, suggesting that IgGRF is much more reactive at lower temperatures. In contrast, the interaction of IgARF and IgMRF with IgG at 6 degrees C was similar to that at 30 degrees C. The association rate constant (k(a)) of IgGRF decreased with an increase in temperature, while those of IgARF and IgMRF were similar under various thermal conditions. The dissociation rate constant (k(d)) of IgGRF was greatly reduced at 25 degrees C, but those of IgARF and IgMRF slightly increased with an increase in temperature. These results suggested that the mode of interaction of IgGRF with IgG differed from in the cases of IgMRF and IgARF. The kinetic properties of the IgGRF-IgG interaction may facilitate elucidation of the IgGRF immune complex formation in rheumatoid joints.
cDNAs encoding geranylgeranyl diphosphate synthase (GGPPS) of two diterpene producing plants, Scoparia dulcis and Croton sublyratus, were isolated using the homology-based polymerase chain reaction method. Both cloned genes showed high amino acid sequence homology (60-70%) to other plant GGPPSs and contained highly conserved aspartate-rich motifs. The obtained clones were functionally expressed in Escherichia coli and showed sufficient GGPPS activity to catalyze the condensation of farnesyl diphosphate (FPP) and isopentenyl diphosphate to form geranylgeranyl diphosphate. To investigate the factor determining the product chain length of plant GGPPSs, S. dulcis GGPPS mutants in which either the small amino acids at the fourth and fifth positions before the first aspartate-rich motif (FARM) were replaced with aromatic amino acids or in which two additional amino acids in FARM were deleted were constructed. Both mutants behaved like FPPS-like enzymes and almost exclusively produced FPP when dimethylallyl diphosphate was used as a primer substrate, and failed to accept FPP as a primer substrate. These results indicate that both small amino acids at the fourth and fifth positions before FARM and the amino acid insertion in FARM play essential roles in product length determination in plant GGPPSs.
The relationship between limb loading and lower-leg electromyographic (EMG) activity was examined during orthotic locomotion in a complete paraplegic patient. The level of limb loading was modified by a hanging system. Surface EMG in the lower-leg extensor and flexor muscles was unilaterally recorded together with the load signal on the ipsilateral sole. The motion of the knee and the ankle joints was minimized, which means that the change in length of the examined muscles was minimum. The muscles were activated synchronously with the locomotor movement and the magnitude of the extensor activity was changed relative to the peak load on the sole. It is conceivable that the spinal cord interpreted the load information and modified the EMG output in the anti-gravity muscles even in the absence of stretch reflexes.
The concentrations of phosphate metabolites were measured in perfused rabbit ovaries before, during and after ischemia, and during the ovulatory process induced by the administration of pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (HCG) using 31P NMR spectroscopy. A decrease in adenosine triphosphate (ATP) and an increase in inorganic phosphate (Pi) during ischemia were observed. After reperfusion of the ovary, both ATP and Pi levels returned to their initial control levels. These results are in agreement with the results observed in other organ tissues. On the other hand, ATP levels rapidly decreased dose dependently with infusion of HCG during 10 h of perfusion. A decrease in ovarian ATP concentration after infusion of HCG was also confirmed by enzymatic analysis of the extracts from ovarian tissues. On the other hand, significant changes in Pi levels were not observed throughout the perfusion period. Furthermore, significant changes in phosphomonoester (PME) levels, adenosine diphosphate (ADP) levels and intracellular pH were not observed before and during the infusion of HCG. The concentration of cyclic adenosine 3',5'-monophosphate (cAMP) in the perfusate after the perfusion was also measured during the ovulatory period. Within 30 min cAMP significantly increased dose dependently and reached peak levels within 60 min. The concentration of cAMP then gradually decreased. Ovulatory efficacy during the infusion of HCG was also observed. These results suggest that the decreased ATP in the successive processes leading to ovulation probably reflects protein phosphorylation through the activation of the cAMP-dependent protein kinases prior to induction of various chemical reactions related to the initiation of ovulation.
A rare case of diaphragm hernia containing an accessory spleen and great omentum is reported. Tc-99m phytate SPECT showed tracer accumulation in the accessory spleen and was useful in the evaluation of the disease.
We report a rare case of unusual widening of perivascular spaces (Virchow-Robin spaces). MR images showed multiple small round cystic areas along the perforating medullary arteries with signal intensity identical to the cerebrospinal fluid predominantly in the right cerebral white matter. Tc-99m HMPAO SPECT images showed no remarkable laterality and no definite ischemic lesion, and the neurological status of the patient was not remarkable. MR was a diagnostic examination and Tc-99m HMPAO SPECT was a useful supplementary examination in the evaluation of this case of unusual widening of Virchow-Robin spaces.
BACKGROUND/AIMS: Hepatitis B virus (HBV) quasispecies have been detected in patients with chronic hepatitis B. In order to elucidate the relationship between HBV mutation and liver cell necrosis in situ, we analyzed sublobule-sized specimens microdissected from formalin-fixed paraffin-embedded liver biopsy tissues taken from patients with chronic hepatitis B. METHODS: The subjects were 20 patients with chronic hepatitis B. We extracted HBV-DNA from two sublobular regions of HBV-infected liver biopsy tissue, those with the most severe and the mildest hepatitis activity, demonstrated microscopically. The DNA coding sequence of the precore-core region of HBV was determined by amplifying the DNA by the polymerase chain reaction, followed by direct sequencing. RESULTS: In all seven patients with minimal to mild hepatitis activity, but only 4 of 13 with moderate to severe activity, the amino acid sequence of the precore-core region of HBV obtained from the region with the most severe hepatitis activity showed over 99% homology with the corresponding sequence of HBV obtained from region with the mildest hepatitis activity (p<0.05). CONCLUSION: The differences between intrahepatic HBVs observed in patients with highly active hepatitis suggest that exacerbation of hepatitis in vivo is related to the appearance of variants in the precore-core region of HBV.
To elucidate the physiological role of Fyn, we analysed the properties of synaptic transmission and synaptic plasticity in hippocampal slices of mice overexpressing either wild-type Fyn (w-Fyn) or its constitutively active mutant (m-Fyn). These fyn-transgenes were driven by the calcium/calmodulin-dependent protein kinase II alpha promoter which turned on in the forebrain neurons including hippocampal pyramidal cells and in late neural development. In the hippocampal slices expressing m-Fyn the paired-pulse facilitation was reduced and the basal synaptic transmission was enhanced. A weak theta-burst stimulation, which was subthreshold for the induction of long-term potentiation (LTP) in control slices, elicited LTP in CA1 region of the slices expressing m-Fyn. When a relatively strong stimulation was applied, the magnitude of LTP in m-Fyn slices was similar to that in control slices. By contrast, the basal synaptic transmission and the threshold for the induction of LTP were not altered in the slices overexpressing wild-type Fyn. To examine the effect of expression of m-Fyn on GABAergic inhibitory system, we applied bicuculline, a GABAA receptor blocker, to the hippocampal slices. The ability of bicuculline to enhance excitatory postsynaptic potentials was attenuated in slices expressing m-Fyn, suggesting that the overexpression of m-Fyn reduced the GABAergic inhibition. The enhancement of synaptic transmission and the reduction of GABAergic inhibition may contribute to the enhanced seizure susceptibility in the mice expressing m-Fyn. Thus, these results suggest that regulation of Fyn tyrosine kinase activity is important for both synaptic transmission and plasticity.
The sialyl-Tn (sTn) antigen is a well known cancer-associated antigen, the expression of which is related to the prognosis of cancer patients. We aimed to isolate a human gene encoding an N -acetylgalactosamine alpha2,6-sialyltransferase which synthesizes sTn antigen, and to characterize the enzyme. Degenerate primers encoding sialyl motifs were used for the polymerase chain reaction to amplify complementary DNAs prepared from RNAs of human pyloric mucosae with intestinal metaplasia, which abundantly expressed sTn antigen, followed by screening of full-length cDNAs using the amplified DNA fragment as a probe. We isolated two human cDNA clones, long-form (2.46 kb) and short-form (2.23 kb) cDNAs. The former encodes an active enzyme with a predicted 600 amino acid sequence. The latter, a splice-variant of the long-form, encodes an inactive enzyme. HCT15 human colorectal cancer cells stably expressing the long-form cDNA expressed sTn epitopes on O -glycans. The long form cDNA was considered to encode a human homologue of chick ST6GalNAc I for the following reasons: (1) the putative amino acid sequence showed greater homology to that of chick ST6GalNAc I (55%) compared to other sialyltransferases, (2) it encodes the extraordinarily long stem region that is a typical feature of chick ST6GalNAc I, and (3) the substrate specificity was very similar to that of chick ST6GalNAc I. In situ hybridization demonstrated that the localization of transcripts correlated well with that of sTn antigen in gastric cancer cells and Goblet cells in intestinal metaplastic glands. Thus, we determined that the long-form cDNA of the human ST6GalNAc I gene encodes the probable candidate for the human sTn synthase(s).
Hepatic stellate cells (HSCs) were changed in their morphology, proliferative activity, and functions by culturing on type I collagen gel, as compared to the culture on polystyrene surface. HSCs have been found to produce extracellular matrix components and matrix metalloproteinases (MMPs). In this study, we have assessed the effects of several types of substrata on the expression of MMPs in HSC culture. MMP-1 expression was detectable in HSC culture on polystyrene surface and on type I collagen gel by immunofluorescence staining and reverse transcriptase-polymerase chain reaction (RT-PCR). The results from in situ zymography revealed the presence of interstitial collagenase activity around HSCs and along their cellular processes. Although proMMP-2 and proMMP-9 were detectable by gelatin zymography in the conditioned medium from both cultures using type I collagen gel and Matrigel as substratum, an active form of MMP-2 but not of MMP-9 was detected only in the culture using type I collagen as a substratum. Tissue inhibitor of metalloproteinase-2 expression was observed by RT-PCR in HSCs cultured on or in type I collagen gel, suggesting the suppression of MMP-2 activity detected in HSC culture using type I collagen. These results indicate a differential expression of MMP activity, hence the remodeling of extracellular matrix components is dependent on the substratum used for HSC culture. The HSC culture using several types of substrata appears to be a useful in vitro model to study the mechanism of extracellular matrix remodeling.
The incisor development of fetal rats on gestation day 19 was well correlated with their fetal weights. The number of odontoblasts in the mandibular incisors, an index of incisor development, increased more than that of the maxillary incisors with increase in fetal body weights. Maternal acetazolamide treatments were observed to suppress the mean fetal weight and to retard incisor development. A smaller incisor size, a thinner predentin layer, and fewer odontoblasts were characteristic of the acetazolamide group. There was also a good correlation between the fetal weights and the number of odontoblasts in the acetazolamide group. From these results, we postulated that the retarded incisor development of the fetal rats caused by the maternal acetazolamide treatment was related to their suppressed fetal weights. However, the regression coefficient of the fetal weights and the number of odontoblasts in the acetazolamide group was smaller than that of the vehicle control group. It may indicate that retarded incisor development in response to maternal acetazolamide treatment is to some extent independent of suppressed fetal weight.
OBJECTIVE: We compared early-phase CT with late-phase CT in the evaluation of pancreatic adenocarcinoma. MATERIALS AND METHODS: Both early- and late-phase CT images of 25 pancreatic adenocarcinomas were compared with surgical-pathologic findings. We evaluated tumor detectability, tumor size, and local tumor invasion. RESULTS: Tumor detectability was 96% on early-phase CT imaging and 64% on late-phase CT imaging (p < .01). Sensitivity for anterior serosal invasion, retroperitoneal invasion, and arterial invasion on early-phase CT exceeded sensitivity on late-phase CT (p < .05). However, specificity for all factors on early-phase CT was less than or equal to specificity on late-phase CT. The grade of local tumor invasion on early-phase CT achieved better agreement with the surgical-pathologic results than did late-phase CT, especially for tumor size and retroperitoneal invasion. CONCLUSION: Early-phase CT was better than late-phase CT in revealing tumors, tumor size, and retroperitoneal invasion.
We analyzed 58 cases of advanced or recurrent cervical cancer treated with intra-arterial infusion chemotherapy (IAIC) with or without radiotherapy. Two separate IAIC regimens were administered since 1985: group I consisted of 5-FU + MMC +/- ADR (30 patients) and group II consisted of CDDP + MMC +/- 5-FU (28 patients). The tip of a catheter was placed in the bifurcation of the abdominal aorta (1 way method: 45 patients regimen II: 15) between 1977-1984. We have used selective catheterization (2 ways method: 9) since 1995 in order to get good drug distribution. However we experienced grade 4 toxic effect of cutaneous and pain with this method, so we have used a 3 ways method (4 patients) since 1998. The two-year survival rete was 60% with the 1 way method, and 67% with the 2 ways method and regimen II. Severe adverse effects (grade 3 + 4) were found in 53, 56, 0%, respectively, by each of the three methods (1, 2, 3 ways) hematologically, 13, 22, 0% in gastrointestinally, 0, 44, 0% in cutaneously and 0, 56, 0% in pain or neurotoxicity. These data suggest that IAIC by the 3 ways method is a useful treatment for advanced or recurrent cervical cancer. However, one should check the blood flow distribution periodically, and control concentration of drugs.