Biomedical subjects
Publications and source records attributed to T Baba.
An AIDS patient with the cardinal complaint of severe pigmentation on the face is reported. Hyperpigmentation is an unusual symptom of AIDS. This is a Japanese patient who presented melanosis Riehl-like discoloration. The importance of pigmented lesions in patients who have not been given any anti-HIV agents has not been emphasized in the literature.
A point mutation in the N-acetyltransferase gene (NAT2) leads to the recessive trait for the slow acetylator phenotype, which is suggested to be associated with microalbuminuria in Type 1 diabetic patients. Our study was designed to elucidate whether the NAT2 gene polymorphism would be a marker for diabetic nephropathy. The genotype distribution was studied in Japanese Type 2 diabetic patients with established nephropathy (n = 43), with microalbuminuria (n = 24), with normoalbuminuria (n = 18), non-diabetic patients with kidney disease (n = 62), and healthy control subjects (n = 51). The different alleles of the NAT2 gene were identified by restriction fragment length polymorphism analysis: the gene was amplified from genomic DNA (obtained from blood) and digested with restriction enzymes. The genotype was classified by the specific pattern of each allele (M1, M2, M3) in the agarose electrophoresis and ethdium bromide fluorescence. Alleles M1, M2, and M3 of NAT2 gene were found in 42.4% of all subjects (40.0% in all diabetic patients and 44.2% in all non-diabetic controls). The prevalence of the genotype, encoding the slow acetylator phenotype, was 7.0% in diabetic patients with established diabetic nephropathy, 20.8% in microalbuminuric diabetic patients, 0% in normoalbuminuric diabetic patients, 6.5% in non-diabetic patients with kidney disease, and 7.8% in healthy control subjects. The differences in the prevalence were non-significant. The results suggest that the N-acetyltransferase gene polymorphism may not be a genetic risk marker for diabetic nephropathy in Japanese Type 2 diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Sustained VT in two patients was terminated by intravenous administration of dipyridamole, an adenosine transport inhibitor. VT was induced by rapid atrial or ventricular pacing, isoproterenol, or dibutyryl cyclic AMP infusion, or exercise. VT also was aborted by adenosine triphosphate or acetylcholine injection, or by vagal stimulation. VT was terminated or prevented by verapamil or propranolol. In addition, arrhythmias were prevented by oral administration of dipyridamole. These results suggest that VT is due to cyclic AMP-mediated triggered activity and that inhibition by dipyridamole may be due to a reduction in the intracellular concentration of cyclic AMP.
Bacillus stearothermophilus 21 is a gram-positive, facultative thermophilic aerobe that can utilize xylan as a sole source of carbon. We isolated this strain from soil, purified its extracellular xylanase and beta-xylosidase, and analyzed the two-step degradation of xylan by these enzymes (T. Nanmori, T. Watanabe, R. Shinke, A. Kohno, and Y. Kawamura, J. Bacteriol. 172:6669-6672, 1990). An Escherichia coli transformant carrying a 4.2-kbp chromosomal segment of this bacterium as a recombinant plasmid was isolated. It excreted active beta-xylosidase and xylanase into the culture medium. The plasmid was introduced into UV-sensitive E. coli CSR603, and its protein products were analyzed by the maxicell method. Proteins harboring beta-xylosidase and xylanase activities were identified, and their molecular masses were estimated by sodium dodecyl sulfate-polyarylamide gel electrophoresis to be 75 and 40 kDa, respectively. The values were identical to those of proteins prepared from cells of B. stearothermophilus 21. The genes for both enzymes were encoded in a 3.4-kbp PstI fragment derived from the 4.2-kbp chromosomal segment. The nucleotide sequence of the 4.2-kbp segment was accordingly determined. The beta-xylosidase gene (xylA) is located upstream of the xylanase gene (xynA) with a possible promoter and a Shine-Dalgarno sequence. The latter gene is preceded by two possible promoters and a Shine-Dalgarno sequence that are located within the 3'-terminal coding region of the former. The two genes thus appear to be, at least partly, expressed independently, which was experimentally confirmed in E. coli by deletion analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
The Escherichia coli heat-stable enterotoxin STp is synthesized as a precursor consisting of pre, pro and mature regions. Mature STp is released into the culture supernatant and is composed of 18-amino-acid resides which contain three intramolecular disulfide bonds. The involvement of DsbA in the formation of the disulfide bonds of STp was examined in this study. A dsbA mutant was transformed with a plasmid harboring the STp gene, and the ST activity was significantly lower than that of the parent strain harboring the same plasmid. Furthermore, purified DsbA induced the conversion of synthetic STp peptide (inactive form) to the active form and increased the ST activity of the culture supernatant derived from the dsbA transformants. These results showed that DsbA directly catalyzes the formation of the disulfide bonds of STp. DsbA is located in periplasmic space, where STp is released as an intermediate form consisting of pro and mature regions. To examine the effect of the pro region on the action of DsbA, we replaced the cysteine residue at position 39 and tested the effect in vivo. The substitution caused a significant decrease of ST activity in the culture supernatant, the accumulation of inactive ST in periplasmic space, and an alteration in the cleavage site of the intermediate of STp. We conclude that Cys-39 is important for recognition by the processing enzymes required for the maturation of STp.
To investigate the pathologic changes of the myocardium and the adverse effects of radiofrequency (RF) catheter ablation, we observed canine hearts that had been ablated by RF energy. Catheter ablation was administered to three sites of the hearts of 46 dogs: endomyocardium, coronary sinus, and atrioventricular junction. The dogs were sacrificed 0-12 weeks after ablation and the lesions were stained with hematoxylin-eosin and Azan stain. Each ablated lesion was well demarcated from the adjacent normal tissue. The margin between the ablated lesion and normal tissue became clearer with time. The lesions were hemispherical and measured about 2 to 10 mm in diameter and 1 to 6 mm in depth. Histologic examination in the acute phase demonstrated the presence of coagulation necrosis of the myocardium, interstitial hemorrhage and edema, followed by infiltration of inflammatory cells. Granulation tissue replaced the normal myocardium. In the chronic phase, the lesions became fibrotic and fatty. A mural thrombus was found in 30% of the cases of endomyocardial ablation and 50% of the right ventricular lesions were transmural. Ablated lesions in the coronary sinus extended to the left atrium and left ventricle. Obstruction of the coronary sinus was observed in 8% of the ablated dogs. Most of the lesions with complete atrioventricular block were ablated at the His penetrating region of the conduction system. Thus, since the ablated lesions were clearly delineated, catheter ablation using RF energy appears to eliminate only the target area.
Insulin resistance is generally interpreted as the physiological state under which insulin causes a reduced glucose-lowering effect. Hyperinsulinaemia is considered to be a result of insulin resistance. Many recent studies have suggested that hyperinsulinaemia and/or insulin resistance is associated with an elevated blood pressure, whereas several other studies have found a modest or no association. Many factors (e.g. adiposity, age, ethnic difference) have been suggested to confound the insulin-blood pressure relationship. Insulin is thought to raise blood pressure by a few possible mechanisms (e.g. stimulating sympathetic nervous system activity, enhancing renal tubular sodium reabsorption). On the other hand, insulin has also been reported to possess a vasodilatory property. Neither an insulin infusion within a physiological range nor continuously sustained hyperinsulinaemia in patients with insulinoma are associated with elevated blood pressure. Therefore, the relationship between insulin and blood pressure is still under discussion. Among the antihypertensive drugs, angiotensin converting enzyme (ACE) inhibitors seem to have marginal effects of improving insulin sensitivity, but whether this effect would lead to a better prognosis for diabetic patients remains to be proven. Lipid lowering drugs appear to show no benefit in lowering blood glucose.
A 68-year-old man with hepatocellular carcinoma complicated by erythrocytosis showed an increased plasma level of immunoreactive erythropoietin (EPO). Northern blot analysis and RT-PCR (reverse transcriptase and polymerase chain reaction) of EPO mRNA extracted from a surgical specimen indicated high expression of EPO mRNA in the tumor tissue. Histological and immunocytochemical examination showed that the tumor was a hepatocellular carcinoma with predominant immunostaining for EPO. The erythrocytosis improved and the high serum EPO level decreased after resection of the tumor. This is the first demonstration of EPO mRNA expression in hepatocellular carcinoma tissue by RT-PCR.
OBJECTIVE: To evaluate the effect of gastric emptying on postprandial insulin requirement in insulin-dependent diabetes mellitus (IDDM) patients with and without gastroparesis. RESEARCH DESIGN AND METHODS: Postprandial insulin requirement and gastric emptying were simultaneously evaluated in five IDDM patients with gastroparesis and in six control IDDM patients without gastroparesis. Postprandial insulin requirement after test-meal intake was assessed by measuring the insulin infusion rate during a 4-h feedback control with an artificial endocrine pancreas device (Biostator, Life Science Instruments, Miles, Elkhart, IN). Gastric solid and liquid emptyings were evaluated during the Biostator study by measuring the disappearance rate of 99mTc in the stomach and in the time course of plasma acetaminophen concentration, respectively. RESULTS: Total insulin requirement during the first 120 min after the test-meal intake was significantly lower in the gastroparetic patients than in the control patients. The gastroparetic patients showed no apparent postprandial peak for insulin infusion rate during the 4-h study, although the peak rate was observed within 120 min after the test-meal intake in the control patients. The disappearance of 99mTc in the stomach was significantly slower, and plasma acetaminophen concentrations were significantly lower in the gastroparetic patients compared with those in the control patients, respectively. CONCLUSIONS: The results suggest that IDDM patients with gastroparesis, accompanied by impaired solid and liquid emptying, have an altered postprandial insulin requirement.
Leukotriene C4 (LTC4) increases vascular permeability in systemic, brain tumor, and ischemic brain capillaries, but not in normal brain capillaries. This study examines whether the abundance of gamma-glutamyl transpeptidase (gamma-GTP) in normal brain capillaries might act as an enzymatic barrier to vasoactive leukotrienes in the brain. Blood-brain barrier (BBB) permeability was determined by quantitative autoradiography using 14C-aminoisobutyric acid. Ischemia was produced by occluding the middle cerebral artery. Seventy-two hours after occlusion, gamma-GTP activity in ischemic brain disappeared, and LTC4 (4-micrograms total dose), which was infused into the carotid artery ipsilateral to the occlusion, selectively increased permeability, Ki, approximately twofold within core ischemic tissue and adjacent tissue, compared to vehicle alone in seven brains (15.53 +/- 6.03 vs. 7.29 +/- 3.36, p < 0.05, and 8.76 +/- 4.02 vs. 4.32 +/- 2.65, p < 0.05, respectively). No effect on BBB was seen in nonischemic brain tissue. Twenty-four hours postocclusion, gamma-GTP activity was still present, and LTC4 infusion did not increase permeability within ischemic tissue. However, inhibition of gamma-GTP with acivicin allowed LTC4 to increase permeability even 24 hours after occlusion in ischemic core and adjacent tissue compared to vehicle alone in seven brains (17.21 +/- 16.32 vs. 8.23 +/- 6.58, p < 0.05, and 11.78 +/- 7.96 vs. 4.56 +/- 1.93, p < 0.01, respectively). Acivicin almost completely blocked both the histochemical activity of gamma-GTP in brain capillaries and the metabolism of LTC4 in isolated bovine capillaries. These findings suggest that gamma-GTP may help normal brain capillaries resist the vasoactive effects of LTC4. In contrast, gamma-GTP is lost in injured brain capillaries, which allows LTC4 (in combination with other factors) to increase vascular permeability in ischemic brain and brain tumors.
The aim of this study was to determine if upper gut function and pancreatic exocrine secretion are affected by the presence of unabsorbed carbohydrate in the distal ileum. In this investigation, starch or glucose was perfused into the canine ileum. This study showed that ileal perfusion of both starch and glucose delayed gastric emptying and prolonged small bowel transit time. Furthermore, glucose had greater effects on gastrointestinal transit time than starch. In contrast, amylase output was increased by ileal perfusion of starch, but was not affected by that of glucose. Our results suggest that the ileal regulation of gastrointestinal transit and amylase output could be mediated by different mechanisms.
A cDNA clone encoding maize branching enzyme II (BEII) has been independently isolated from a maize endosperm cDNA library. The deduced protein sequence of maize BEII was compared with that of BE from diverse sources. The gene encoding mature BEII of maize endosperm has been expressed in E. coli using the T7 promoter. The expressed BEII was purified to near homogeneity so that amylolytic activity and bacterial BE could be completely eliminated from the BE preparation. The expressed enzyme showed very similar properties to those of BEII purified from developing maize endosperm. This result confirmed our earlier report that BEII had a lower rate of branching amylose and the rate of branching amylopectin was twice that of branching amylose. This study also showed a greater advantage of purifying BEII from the bacterial expression system than from developing maize endosperm. Most importantly, this study has established a useful tool to study the structure-function relationships of the maize BE using site-directed mutagenesis.
Effects of prostaglandin E1 (PGE1) on liver function were studied in 72 patients who underwent mitral valve replacement (MVR) and coronary artery bypass grafting (CABG). The patients were divided into three groups: (A) patients with preoperative hepatic dysfunction who underwent MVR; (B) patients without previous hepatic dysfunction who underwent MVR; (C) patients without hepatic dysfunction who underwent CABG. About half of the patients in each group received PGE1 during the operation and postoperative period in the ICU. Change of serum GOT, GPT, albumin, total bilirubin, and cholinesterase (ChE) showed no difference between the patients with and without PGE1 administration in groups B and C. But, in group A, PGE1 administration significantly ameliorated the decrease of ChE, a condition which is usually observed in the first and second postoperative weeks after MVR. None of the patients showed severe hepatic dysfunction in the PGE1 group. One patient in the control group A revealed severe hepatic failure with high bilirubinemia and decreased ChE. These results suggest that the administration of PGE1 to patients with hepatic dysfunction, scheduled for MVR, might protect the liver from deterioration.
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Histiocytosis X is a disease of unknown etiology, characterized by a mass of proliferating histiocytes, plasma cells and inflammatory cells foaming a granuloma within the reticuloendothelial elements of any organ in the body. In the central nervous system (CNS), hypothalamic disorder of histiocytosis X is often found, but histiocytosis X in other regions is quite rare. We report a case of a 5-year-old girl with histiocytosis X of the zygoma presenting as a mass lesion in the tentorium cerebelli. A computed tomographic (CT) scan demonstrated a tumor at the left tentorial region, extending along the dura mater of the tentorium cerebelli. Magnetic resonance imaging (MRI) revealed a low signal intensity region on both T1 and T2-weighted images. MRI with Gd-DTPA showed a homogeneous enhanced mass extending to right and inferior sites with a thickened tentorium. As the thickened dura matter continued from the left middle fossa to the mass lesion, the tumor was considered to arise from the left zygoma and extend to the tentorium cerebelli. CNS extension of histiocytosis X is manifested either as (1) the cerebral type or (2) the dural type. Many cases of cerebral type histiocytosis X including hypothalamic disorder have been reported. Only 6 cases of the dural type of histiocytosis X have been described. Although the lesions of the cerebral type of histiocytosis X show prolonged T1 and T2 values on MRI, the MRI findings of the dural type have not been reported. The present case is the first report of the appearance of the lesion on MRI.(ABSTRACT TRUNCATED AT 250 WORDS)
We have previously found that an antigenic protein specific for C3H strain mouse (C3H strain-specific antigen, CSA) is identical to peptide-binding protein 74 (PBP74). PBP74/CSA is a novel member of the stress-70 protein family in mitochondria. In this study, mouse genomic clones encoding PBP74/CSA, including the 5'- and 3'-flanking regions of the gene, have been isolated and sequenced. The PBP74/CSA gene contained 17 exons interrupted by 16 introns. Two dimeric repeats of the consensus sequence of the heat-shock element are present in the 5'-flanking region of the PBP74/CSA gene. Moreover, the first intron is interrupted within the amino-terminal leader sequence, the pattern of which is similar to that of cytochrome c1 located in the mitochondria.
The human cytochrome P450 (P450) 2C gene family is complex and heterologous expression methods are needed to facilitate the isolation of individual P450 proteins and the elucidation of their catalytic specificities. We prepared a series of constructs of P450 2C10 in the plasmid vector pCW, with modification of the 5' end of the coding sequence of the cDNA. Some were not expressed at all in Escherichia coli; two were expressed at levels of 5-20 nmol membrane-bound P450 (liter culture)-1--one (2C1028) with original codons 2-7 altered by substitution of the 5'-terminal sequence described by Barnes et al. (Barnes, H. J., Arlotto, M. P., and Waterman, M. R., Proc., Natl. Acad. Sci. USA 88, 5597-5601, 1991) and one (2C1029) with original codon 2 modified, codons 3-20 deleted, and alteration of the immediate downstream codons. In both cases the P450 2C10 proteins were found essentially only in the bacterial membranes. These proteins could be purified to a high degree by solubilization and a single DEAE chromatography step. Typical P450 Fe2+.CO absorption spectra were observed in the bacterial membranes and the purified preparations. The P450 2C1029 protein was found to have its N-terminal Met removed and the expected residues 2 (Ala)-24 were identified by amino acid sequence analysis. However, the other P450 (2C1028) was apparently blocked at the N-terminus. Three native P450 2C9/10 preparations isolated from human liver showed the expected sequences (beginning with Met) for at least the first 17 residues. The blocked N-terminus in the P450 2C1028 protein may be the result of the MALLLAVF sequence, which was also used in the expression of P450 3A4 and resulted in a blocked protein. Catalytic activities of P450 2C1028 and P450 2C1029 for tolbutamide hydroxylation were similar to those measured with purified liver P450 C29/10 in the presence of cytochrome b5, although the effect of cytochrome b5 did not always show the same pattern as with the isolated liver enzyme. The recombinant P450 2C10 enzymes did not catalyze (S)-mephenytoin 4'-hydroxylation.
A 38-kDa protein, sp38, was purified from the detergent extract of porcine epididymal sperm. Sp38 showed zona pellucida-binding properties similar to those of proacrosin. These two proteins specifically bound to the 90-kDa glycoprotein form of the zona pellucida components in a calcium-dependent manner. The binding of sp38 to the zona pellucida glycoprotein was inhibited by proacrosin. These findings suggest that the two proteins competitively interact with the zona pellucida during the early stage of fertilization.