Localization of a candidate colon tumor-suppressor gene (DRA) to 7q22-q31.1 by fluorescence in situ hybridization.
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Chromosome Mapping↗
Biomedical subjects
T Taguchi
Publications and source records attributed to T Taguchi.
Cytogenetic analysis of 63 non-small cell lung carcinomas: recurrent chromosome alterations amid frequent and widespread genomic upheaval.
A detailed cytogenetic analysis of 63 non-small cell lung carcinomas (NSCLCs) was carried out for identification of recurrent chromosomal alterations. Most specimens displayed very complex karyotypes with multiple numerical and structural changes (median number, 31). Losses of chromosomes 9 (65% of cases) and 13 (71%) were the most frequent numerical changes. Loss of the Y was often observed in tumors from males. Gain of chromosome 7 was also frequent (41%). Chromosome arms 1p, 1q, 3p, 3q, 6q, 7q, 8q, 9p, 11q, 17p, and 19q were particularly prone to rearrangement. The chromosome arm most often contributing to losses was 9p (79%). Other arms that were frequently lost included 3p, 6q, 8p, 9q, 13q, 17p, 18q, 19p, 21q, 22q, and the short arm of each acrocentric chromosome. The percentage of cases with loss of 3p was significantly higher in squamous cell carcinomas (94%) than in adenocarcinomas (60%). There was also a statistically significant increase in the proportion of cases with gains of 1q, 7p, and 11q in adenocarcinomas compared to squamous cell carcinomas. Several recurrent isochromosomes and unbalanced exchanges were found. Among these was i(5p), which was observed in nine tumors, eight of which displayed adenomatous features. An i(8q) was identified in six cases, including five adenocarcinomas. Double minutes and/or homogeneously staining regions were seen in seven specimens. These data indicate that numerous chromosome alterations contribute to the pathogenesis of NSCLC and that, amid this widespread genomic disarray, recurrent abnormalities exist that could have biological and clinical implications.
Adult↗
In situ localization of type III and type IV collagen-expressing cells in human diabetic nephropathy.
Nodular intercapillary glomerulosclerosis is the most typical lesion of diabetic nephropathy (DN) and is characterized by increased extracellular matrix (ECM) and amorphous masses of mesangial matrix. The local exaggeration of these deposits results in the formation of the typical diabetic nodule. To clarify the composition of the ECM of sclerotic lesions in DN, we investigated the distribution of type III and type IV collagens and their mRNAs by immunohistochemistry and in situ hybridization, respectively. In normal renal tissues, there was no intraglomerular immunostaining for type III collagen, while strongly positive staining was found in the extraglomerular interstitium. Positive immunostaining for type IV collagen was also present in the mesangium, glomerular basement membrane (GBM), Bowman's capsule, and the vascular pole of the normal glomerulus. In DN, the nodular lesions were negative for type III collagen and strongly positive for type IV collagen. On the other hand, in the late stage of global sclerosis, both type III and type IV collagens were diffusely present in the sclerotic matrix. To determine the origins of these type III and type IV collagens in the sclerotic matrix, in situ hybridization was performed, utilizing thymine-thymine (T-T) dimerized synthetic oligonucleotides complementary to either pro alpha 1(III) chain or pro alpha 1(IV) chain mRNAs as probes. The signals were detected by enzyme immunohistochemistry using an anti-T-T antibody. Intraglomerular cells (glomerular epithelial and mesangial cells) containing type III collagen mRNA were found in DN with sclerotic lesions, but not in normal glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS)
Collagen↗
Effects of naftidrofuryl oxalate on microsphere-induced changes in acetylcholine and amino acid content of rat brain regions.
Effects of naftidrofuryl oxalate (naftidrofuryl) on neurotransmitter, acetylcholine, and amino acid content of brain regions following microsphere-induced cerebral embolism were examined to elucidate its possible therapeutic effects on ischemic brain. Rats received 900 microspheres (48 microns in diameter) via the right internal carotid artery, followed by ligation of the right common carotid artery; and histological and biochemical alterations were examined on the 3rd, 5th, and 28th days after embolism. The embolism induced increases in triphenyltetrazolium chloride- (TTC)-unstained areas and decreases in acetylcholine, glutamate, aspartate, and gamma-aminobutyric acid (GABA) contents in the cerebral cortex, striatum, and hippocampus of the right hemisphere, suggesting that microsphere embolism causes severe damage to these brain regions. Hematoxylin-eosin staining of the right cortical sections after embolism showed degeneration and necrosis of nerve cells with chromatolytic nuclei and eosinophilic cytoplasm. Changes in neurotransmitters of the left hemisphere were relatively small. Treatment with naftidrofuryl of the embolized rats with stroke-like symptoms took place from postoperative day 1 to 28. Treatment resulted in a reduction in TTC-unstained areas, less morphological damage to cerebral cortex on the 3rd and 5th days, and an appreciable restoration of acetylcholine content of three brain regions of the right hemisphere throughout the experiment, but restoration of neurotransmitter amino acids was observed to a smaller degree. The results suggest that naftidrofuryl is capable of preventing the development of ischemia-induced, sustained damage to brain regions vulnerable to oxygen deficiency, particularly by improving impaired acetylcholine metabolism.
Acetylcholine↗
Use of human leukocyte antigen-mismatched allogeneic lymphokine-activated killer cells and interleukin-2 in the adoptive immunotherapy of patients with malignancies.
Clinical effects and side effects were studied in the adoptive immunotherapy of patients bearing malignant diseases using human leukocyte antigen (HLA)-mismatched allogeneic lymphokine-activated killer (LAK) cells. Allogeneic LAK cells were induced from peripheral blood lymphocytes (PBL) of normal donors by means of initial stimulation with pokeweed mitogen (PWM). Six of 15 patients applied in the adoptive immunotherapy showed clinical effects such as partial or complete regression of pulmonary metastasis, pleural effusion and primary tumor. All pulmonary metastatic lesions were eliminated in one case by this adoptive immunotherapy combined with chemotherapy. Generally toxic effects were chillness, fever and general fatigue which were reversible, and no allergic side effects occurred even though allogeneic LAK cells were injected frequently except one patient who showed preshock like symptom accompanied with leukocytopenia and continuous hypotension immediately after infusion but was finally rescued. In the patients who received more than 10(11) of allogeneic LAK cells, anti-HLA class I antibodies appeared without any evidence of autoantibody. However, immunological side effects were never experienced after injection of allogeneic LAK cells even when the anti-HLA class I antibodies appeared in the patients. Taken together, allogeneic LAK cells could be considered as alternative therapy for patients with malignancies who could not supply sufficient materials of autologous LAK cells.
Adult↗
Glomerular expression of type III and type IV collagens in benign nephrosclerosis: immunohistochemical and in situ hybridization study.
The development of glomerular sclerosis in benign nephrosclerosis (BNS) was studied. We investigated the intraglomerular expression of type III and IV collagens and their mRNAs by immunohistochemistry and by the in situ hybridization method. Formalin-fixed paraffin sections from 28 patients with BNS and 10 control cases were stained by the avidin-biotin complex (ABC) method using monoclonal antibodies for human type III and IV collagens. In the course of the sclerotic process of the glomerulus in BNS, the glomerular staining intensity of type IV collagen increased. The strongest staining was observed in the glomerulus at the early sclerotic stage, and intensity decreased slightly at the later stages. Although type III collagen was absent in normal and nonsclerotic glomeruli, peripheral regions of the sclerotic glomeruli were positive at the early sclerotic stage. Later, type III collagen was diffusely observed in the completely hyalinized glomeruli. The expression of type III and type IV collagen mRNAs was detected in the glomeruli of BNS by the non-radioactive in situ hybridization method using thymine-thymine (T-T) dimerized synthetic oligonucleotides. The number of mRNA positive cells for type III and type IV collagens increased at the presclerotic and early sclerotic stages. But these cells gradually decreased in number as glomerular sclerosis developed. We concluded that type III collagen was presumably synthesized by the intraglomerular cells and may contribute to the development of glomerular sclerosis in BNS along with type IV collagen.
Adult↗
Abnormally shaped arteries in the intestine of children with Hirschsprung's disease: etiological considerations relating to ischemic theory.
Abnormally shaped arteries were found in the intestines of 17 of 62 patients (27%) with Hirschsprung's disease. The histological characteristics of abnormal arteries included proliferation of collagen fibers and smooth muscle cells in the adventitia. The incidence of abnormal arteries in each type of aganglionosis was as follows: 25% (13 of 51) in short-segment aganglionosis; 0% (0 of 6) in long-segment aganglionosis; and 80% (4 of 5) in total-colon or extensive aganglionosis. The older the patients were at the time of resection, the higher the incidence of abnormal arteries (< 1 year old, 15%; 1-3 years old, 38%; > 3 years old, 75%). The abnormally shaped arteries were mostly located in the histological transitional zone. These findings suggest the following possibilities: (a) the craniocaudal migration of ganglion cells was interrupted by intestinal ischemia in the presence of abnormal arteries in utero; (b) an ischemic episode caused both the disappearance of neural cells and dysplasia of the artery; (c) the ganglion cells were destroyed by mild ischemia caused by the abnormal arteries; or (d) the tension caused by mechanical expansion resulted in a change in the vascular walls in the transitional zone.
Adolescent↗
Adenine nucleotide metabolism in relation to graft viability in rat small-bowel transplantation.
The relation between the level of cellular adenine nucleotides and graft viability after cold preservation and warm ischemia was studied by using a rat small-bowel transplantation model. The rat jejunum was preserved in lactated Ringer's solution at 4 degrees C for 120 min, and was then transplanted syngeneically under warm ischemia after between 60 and 180 min. The recovery levels of ATP and the energy charge at 30 min after reperfusion in the viable graft were significantly higher than those in the nonviable graft. None of the grafts were viable when the recovery level of ATP at 30 min after reperfusion was less than 2.8 mumol/g dry weight. These results suggest that the recovery level of ATP at 30 min after reperfusion is a reliable parameter for graft viability in small-bowel transplantation.
Adenine Nucleotides↗
Renal pathology in patients with reflux nephropathy. The turning point in irreversible renal disease.
In reflux nephropathy both interstitial and glomerular damage advances with an increase in the scarring grade even in macroscopically normal regions. Based on various histologic findings, sclerosis and the enlargement of glomeruli rapidly accelerate between stages c-a and c-b, as shown by the combined Smellie's scarring grade of the bilateral kidneys. These two steep histologic changes in stage c-b are followed by a remarkable reduction in renal function (DTPA-GFR) and an increase in the amount of urinary protein. These clinicopathological changes thus suggest that hemodynamic changes or overloading in the functional remnant nephrons possibly start in stage c-a. It is also suggested that glomerular enlargement is an index of progressive disease in reflux nephropathy. Among our specimens, most cases of glomerular sclerosis were global while focal segmental glomerulosclerosis was very rare. These findings thus suggest that the global sclerosis observed in our specimens is clearly different from focal segmental glomerulosclerosis.
Adult↗
Amino acids and peptides. XXIII. Leu-enkephalin analogs containing a fluorinated amino acid at position 2, 4 or 5.
Fluorinated analogs of Leu-enkephalin were synthesized by the solution method and the solid-phase method. The synthetic peptides were examined for opioid activities on mouse vas deferens and guinea pig ileum. Among the synthetic peptides,[D-Ala2,Leu(F3)(2R,4S)5]enkephalin and [D-Ala2,Leu(F3)(2S,4R)5]enkephalin exhibited potent opioid activity, and [Leu(F3)(2S,4R)5]enkephalin exhibited high delta-receptor selectivity.
Amino Acid Sequence↗
Simultaneous dual myocardial imaging with iodine-123-beta-methyl iodophenyl-pentadecanoic acid (BMIPP) and thallium-201 in patients with coronary heart disease.
To assess the clinical value of simultaneous dual myocardial imaging with iodine-123-beta-methyl-iodophenyl-pentadecanoic acid (123I-BMIPP) and thallium-201 (201Tl), myocardial imaging was performed at rest and during exercise in seven patients with coronary heart disease. When 123I-BMIPP and 201Tl images were compared, the initial exercise and resting images agreed 87% and 64%, respectively. In the initial resting images, the regional uptake of 123I-BMIPP was frequently less than that of 201Tl. The incidence of exercise-induced reversible defects by 201Tl in the Tl > BMIPP regions was significantly higher than that in the Tl = BMIPP regions (57% vs 4%, p < 0.01) and the incidence of coronary narrowing of more than 90% in the Tl > BMIPP regions was also significantly higher than that in the Tl = BMIPP regions (91% vs 38%, p < 0.01). In addition, this disparity (Tl > BMIPP) was found more frequently in regions with abnormal wall motion than in regions with normal wall motion (hypokinetic regions; 68%, severe hypokinetic or akinetic regions; 50%, vs normokinetic region; 4%, p < 0.01). In contrast, the uptake of 123I-BMIPP correlated closely with that of 201T1 in normal myocardium and the uptake of both 123I-BMIPP and 201Tl was severely reduced in myocardium with severe ischemia during exercise and prior infarction. These results indicate that dual myocardial imaging with 123I-BMIPP and 201Tl may provide a unique means of identifying patients with metabolically disturbed myocardium, such as hibernating and stunned myocardium.
Aged↗
Neurons with intensely negatively charged extracellular matrix in the human visual cortex.
Neurons in the human visual cortex were demonstrated to possess an intensely negatively charged surface coat which was stained with cationic iron colloid and aldehyde fuchsin. Digestion with hyaluronidase eliminated both the iron colloid and fuchsin stainings of the coats. Treatment with chondroitinase ABC, heparitinase and keratanase eliminated the iron colloid staining of the coats, but did not interfere with the fuchsin staining. Electron microscopy of ultrathin sections revealed that the cationic iron particles were preferentially deposited in the perineuronal tissue spaces. These findings indicate that the surface coats consist of sulfated proteoglycans, which, as an extracellular matrix, occupy the perineuronal tissue spaces. This study further demonstrates that neurons with such surface coats are identical with neurons labeled with lectin Vicia villosa agglutinin. The cell surface glycoproteins reactive to this lectin may not be the structural elements of the sulfated coats since the lectin labeling was not interrupted by the hyaluronidase digestion.
Anions↗
Microcirculatory patterns in human pancreas: supplementary observations of vascular casts by scanning electron microscopy.
The blood vascular bed of two human pancreata was replicated partially by arterial perfusion of intentionally reduced amounts of low viscosity methacrylate resin, to be observed with a scanning electron microscope. The findings were compared with those obtained from a pancreas replicated completely by a sufficient amount of resin. Complete replication confirmed our previous findings (MURAKAMI et al., 1992) that many exocrine lobules contained one or more endocrine islets, which preferentially issued insulo-acinar portal vessels continuous with the lobular capillaries. Incomplete replication demonstrated that the casting medium filled blood capillaries in the endocrine islets more promptly than those in the exocrine lobules and secretory ducts. Furthermore, islet-containing lobules allowed a more rapid resin flow to the exocrine tissue via the insulo-acinar portal route than did the lobules lacking an islet. Since the resin medium used had the viscosity of blood and was injected under physiological pressure, the results obtained by the incomplete arterial injections are believed to suggest the physiological state of blood flow in the pancreas.
Adult↗
The occurrence of neurons with strongly negatively charged surface coats in mammalian, avian, reptilian, amphibian and piscine brains.
Neurons with strongly negatively charged surface coats were recognized in mammalian, avian, reptilian, amphibian and piscine brains. Many large-sized neurons had strongly negatively charged surface coats in the visual cortex and brain stem of the cow, cat, guinea pig, mouse, quail and parakeet. Such neurons were also seen in the brain stem of the lower vertebrates such as the house lizard, Japanese terrapin, bullfrog, newt, carp and sweetfish.
Amphibians↗
Chemo-occlusion for the treatment of liver cancer. A new technique using degradable starch microspheres.
The use of particulate embolic agents combined with regional chemotherapy in the treatment of hepatocellular carcinoma and metastatic liver cancer has been widely investigated over the past decade. The rationale for the use of such agents is to provide vascular blockade, resulting in a reduced or halted blood flow. This increases the in situ time, tumour exposure and, thus, efficacy of any coadministered cytotoxic drug. Of all the embolic agents and techniques available, degradable starch microspheres (DSMs) are the agents that have been evaluated most extensively. DSMs are non-toxic, are readily degradable and provide temporary vascular occlusion. Phase II and III clinical trials have demonstrated the efficacy of DSM when coadministered with chemotherapeutic drugs (chemo-occlusion), as measured by tumour response. Indeed, compared with drug therapy alone, a significantly greater tumour response is associated with chemo-occlusion, for patients with either hepatocellular carcinoma or metastatic liver cancer. The use of combination or multi-modular therapies have, in recent years, been investigated. The therapeutic benefits associated with chemo-occlusion would suggest that this technique might have a potential application as an adjuvant, or neoadjuvant therapy, for example, in reducing tumour recurrence after surgical resection in hepatocellular carcinoma, or downstaging a tumour prior to surgical resection, respectively. Furthermore, comprehensive management of patients with liver metastases and potential extrahepatic involvement may well be achieved by a combination of DSM chemo-occlusion and systemic chemotherapy. Large, randomised trials are, however, required to access more fully the clinical benefits associated with chemo-occlusion, such as, quality of life, time to tumour progression and survival. Regionally occlusive techniques administered with cytotoxic agents have also shown potential in the treatment of alternative cancers, for example, breast and pancreatic carcinomas. However, these therapies require further evaluation.
Antineoplastic Agents↗
Changes in the activities of DNA polymerases in growing rat lungs.
We hypothesized that cellular proliferation and the capacity to repair DNA damage in the lung might differ during the pre- and postnatal periods, because the lung is exposed to higher oxygen concentrations and/or various mutagens after birth. In order to test this hypothesis, changes in DNA content and the activities of DNA polymerase alpha and beta were studied in the lungs of 1-day prenatal to 42-day postnatal rats. Total DNA polymerase activity reached its highest level at 1 day prenatal and 1 day after birth. The activity decreased exponentially by 28% up to 14 days of age, a change inversely related to the change in DNA content. The change in total DNA polymerase activity agreed closely with the change in DNA polymerase alpha activity, but not the activity of the beta form, although small elevations in both DNA polymerase alpha and beta were observed on day 3, possibly reflecting the mechanical effect of delivery. The activity of DNA polymerase beta remained relatively constant from 1 day before birth to 21 days after birth, varying by only about 5%. From these results, it is concluded that: (1) cellular proliferation in the lung is most active during the first 2 weeks after birth as supported by the increases in DNA polymerase alpha activity and DNA content, and (2) anticipating the oxygen enriched atmosphere after birth, the level of DNA polymerase beta, involved in the DNA repair system, is already elevated during the prenatal period and remains constant throughout the postnatal period.
Animals↗
Pharmacologic profiles of YM934, a novel potassium channel opener.
Pharmacologic profiles of YM934, a newly synthesized 1,4-benzoxazin derivative K channel opener were evaluated in in vitro and in vivo experiments. In isolated rat portal vein, YM934 and a benzopyran derivative K channel opener lemakalim inhibited the frequency of spontaneous rhythmic contractions concentration dependently, with IC50 values of 14 and 38 nM, respectively. These inhibitory effects were competitively antagonized by glibenclamide (an ATP-sensitive K channel blocker; 10(-7)-3 x 10(-6) M). In isolated rabbit aorta, YM934 (10(-8)-10(-6) M) and lemakalim (10(-8)-10(-6) M) relaxed the contractions induced by 20 mM KCl concentration dependently but were ineffective against the contractions induced by 50 mM KCl. YM934 (10(-8)-3 x 10(-6) M) and lemakalim (3 x 10(-8)-10(-5) M), but not the calcium antagonist nifedipine, relaxed the contractions induced by norepinephrine (NE 10(-6) M) or prostaglandin F2 alpha (PGF2 alpha 3 x 10(-6) M) in the aorta. In pentobarbital-anesthetized dogs, YM934 (1-10 micrograms/kg intravenously, i.v.) dose-dependently increased coronary artery blood flow (CBF), and decreased total peripheral resistance (TPR) and mean blood pressure (MBP). YM934 selectively increased CBF, but had little effect on vertebral, carotid, mesenteric, renal and femoral artery BF. These vasodilatory effects of YM934 were antagonized by glibenclamide. YM934 is a potent K channel opener and possesses potent vasodilatory effects, with particularly pronounced effects on the coronary artery. These effects of YM934 may, like lemakalim, be mediated by opening of ATP-sensitive K channels.
Anesthesia↗
[Recent advance in chemotherapy for breast cancer].
In cases of recurrent progressive breast cancer, ADM, CPM, 5-FU, MTX, MMC and vinca alkaloids have proven to be effective, but CMF and CAF have been considered the standard chemotherapy regimen. But no regimen can cure recurrent progressive breast cancer. Thus, the aim in recent years has been greater efficacy and longer survival by means of dose-intensity. The latter has become possible through G-CSF, the patient's own bone marrow transplant or implantation of peripheral vascular cells and the like, resulting in 70-90% efficacy. The CR rate also has reached over 50%, and long-term survival has been achieved. Clinical research has been thus moving ahead, encouraged by the promise of chemotherapy employing such huge doses. However, in combination with other forms of therapy, a great number of controversial problems are encountered which require study. Recently, a number of agents such as Taxotere or CPT-11 have been used effectively in combination for breast cancer, and they appear to be very promising.
Antineoplastic Agents, Phytogenic↗