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Biomedical subjects

H Handa

Publications and source records attributed to H Handa.

At least 181 records · Page 10Linked to original sources

Cerebral cysticercosis: a case report.

A case of cerebral cysticercosis is reported in a 49-year-old female who presented with headache, nausea, and vomiting. Lumbar CSF showed the findings of mild aseptic meningitis. CT scan revealed an enlargement of the left ambient cistern and a small cystic lesion in the left frontal cortex. MRI demonstrated multilobular cysts in the left ambient cistern with enhancement of their capsules, which compressed and distorted the midbrain. The cysts were surgically excised, and histological examination of the specimen disclosed characteristic features of cysticercus with viable larva. An excellent value of MRI in the diagnosis of intracisternal cysticercosis is emphasized.

Brain Diseases↗

Congenital subclavian steal syndrome with anomaly of the aortic arch.

A case of congenital subclavian steal syndrome associated with an anomalous right-sided aorta is reported. A 41-year-old man complaining of vertigo and a loss of consciousness was admitted. Physical examination revealed a blood pressure differential between the arms that was 20 mm Hg less in the left. Aortography showed a right aortic arch from which arose the right subclavian and both common carotid arteries. The left subclavian artery did not opacify. Right vertebral angiography showed retrograde filling of the left vertebral. A left carotid-subclavian bypass was performed. Postoperatively, the patient is symptom free with equalized blood pressure.

Abnormalities, Multiple↗

cDNA cloning of transcription factor E4TF1 subunits with Ets and notch motifs.

E4TF1 was originally identified as one of the transcription factors responsible for adenovirus E4 gene transcription. It is composed of two subunits, a DNA binding protein with a molecular mass of 60 kDa and a 53-kDa transcription-activating protein. Heterodimerization of these two subunits is essential for the protein to function as a transcription factor. In this study, we identified a new E4TF1 subunit, designated E4TF1-47, which has no DNA binding activity but can associate with E4TF1-60. We then cloned the cDNAs for each of the E4TF1 subunits. E4TF1 was purified, and the partial amino acid sequence of each subunit was determined. The predicted amino acid sequence of each cDNA clone revealed that E4TF1-60 had an ETS domain, which is a DNA binding domain common to ets-related transcription factors. E4TF1-53 had four tandemly repeated notch-ankyrin motifs. The putative cDNA of E4TF1-47 coded almost the same amino acid sequences as E4TF1-53. Three hundred and thirty-two amino acids of the N termini of E4TF1-47 and -53 were identical except for one amino acid insertion in E4TF1-53, and they differ from each other at the C terminus. These three recombinant cDNA clones were expressed in Escherichia coli, and the proteins behaved in the same manner as purified proteins in a gel retardation assay. Nucleotide and predicted amino acid sequences were highly homologous to GABP-alpha and -beta, which is further supported by the observation that GABP-specific antibody can recognize human E4TF1.

Adenoviridae↗

Studies of HIV-1 protease inhibitors. I. Incorporation of a reduced peptide, simple aminoalcohol, and statine analog at the scissile site of substrate sequences.

Inhibitors of the protease of human immunodeficiency virus type-1 (HIV-1) were designed and synthesized. A reduced peptide, simple aminoalcohol, and statine analog, 4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA), were inserted at the scissile site of substrate sequences of HIV-1 protease. While both reduced peptides and simple aminoalcohol derivatives were weak inhibitors, the peptides containing AHPPA demonstrated moderate inhibitory activity. The more potent alcohol configuration of AHPPA is (R), which is opposite to the configuration in potent inhibitors of other aspartic proteases. In particular, compound 28 ((3R,4S)-4-(N-tert-butoxycarbonyl- L-glutaminyl-L-asparaginyl)amino-3-hydroxy-5-phenylpentanoic acid 2'-methylbutylamide) had a Ki of 0.36 microM and exhibited excellent enzyme specificity.

Amino Acid Sequence↗

Studies of HIV-1 protease inhibitors. II. Incorporation of four types of hydroxyethylene dipeptide isosteres at the scissile site of substrate sequences.

Human immunodeficiency virus type 1 (HIV-1) protease inhibitors containing four types of hydroxyethylene dipeptide isosteres were designed and synthesized. These inhibitors consist of eight stereoisomers of phenylalanylproline (Phe-psi[H.E.]-Pro), four stereoisomers of phenylalanylalanine [Phe-psi[H.E.]-Ala), and one stereoisomer each of phenylalanylglycine (Phe-psi[H.E.]-Gly) and cyclohexylalanylalanine (Cha-psi[H.E.]-Ala) hydroxyethylene dipeptide isosteres. For the synthesis of the latter two isosteres, a newly developed synthetic method for gamma-lactone was applied. The inhibitory activities of these peptides were evaluated by cleavage assay of partially purified gag proteins or purified synthetic peptide. Of the inhibitors examined, compounds 2c (Z-Asn-(2S,3R,4S,5S)-Phe-psi[H.E.]-Pro-NHB(un); Bu(n) = n-butyl, Ki = 0.50 microM), 21a (Z-Asn-(2R,4S,5S)-Phe-psi[H.E.]-Ala- NHBu(n), Ki = 0.34 microM) and 23 (Z-Asn-(2R,4S,5S)-Cha-psi[H.E.]-Ala- NHBu(n), Ki = 0.46 microM) were moderately potent inhibitors. The results revealed that the alkyl substituent at C2 is essential, and the stereochemistry of the hydroxyethylene dipeptide isosteres greatly affected their inhibitory activities.

Amino Acid Sequence↗

RNA editing of rapeseed mitochondrial atp9 transcripts: RNA editing changes four amino acids, but termination codon is already encoded by genomic sequence.

The gene encoding subunit 9 of Fo-ATPase of rapeseed mitochondria has been isolated. The complete genomic DNA sequence and cDNA sequence corresponding to the atp9 gene transcript have been determined by a method involving cDNA synthesis, using specific oligonucleotides as primers, followed by PCR amplification, cloning and sequencing of the amplification products. In comparison of cDNA sequences to genomic one, four modifications, C-to-U conversions, have been found. When compared with RNA editing patterns of atp9 transcripts among plant mitochondria, that of rapeseed atp9 transcript is more simple; there are only four editing sites on the coding region, and its termination codon is already encoded by genomic sequence.

Amino Acid Sequence↗

[Complete remission of acute promyelocytic leukemia accompanied by DIC in an elderly patient treated with all-trans retinoic acid].

In this paper we report on a 74-year-old female patient who was suffering from acute promyelocytic leukemia (APL) and who, upon admission to our hospital on February 20, 1992, was also found to be stricken with disseminated intravascular coagulation (DIC). The DIC, however, was quickly arrested by administration of heparin and there was no exacerbation. Also, on admission her peripheral blood leukocyte count was 700/ul, but after oral administration of all-trans retinoic acid (ATRA) (45 mg/m/day) was begun on February 22, this count gradually increased and peaked at 35,200/ul on March 7. Some of these matured leukocytes revealed dysplastic features; some had Auer bodies. At this time cytogenetic analysis of bone marrow cells showed 46XX, t (15;17). The leukocyte count gradually decreased to 1,500/ul, and the dysplastic features disappeared. On March 21 her thrombocytes and reticulocytes began to increase, and she achieved complete remission when her abnormal karyotype disappeared on March 24. She suffered no severe complications such as infection or hemorrhage during treatment. We therefore suggest that ATRA is very effective for APL in elderly patients. It neither exacerbates DIC nor increases the risk of infection. In fact, when ATRA treatment is compared to the standard cytotoxic chemotherapy there is a reduced risk of infection.

Administration, Oral↗

Immortalization of rabbit corneal epithelial cells by a recombinant SV40-adenovirus vector.

PURPOSE: Cultured corneal epithelial cell is detrimental because of its short life span and its heterogeneity. We have tried to establish an immortalized epithelial cell line. METHODS: Primary cultured rabbit corneal epithelial cells were infected with a recombinant SV40-adenovirus vector and were cloned three times. RESULTS: The immortalized cell continued to grow by more than 400 generations through 100 passages. SV40-associated large T antigen was demonstrable on the nuclear membrane of these immortalized cells by immunofluorescence technique. This cell line exhibited a similar cobblestone-like appearance as normal corneal epithelial cells. Transmission electron microscopy showed a line of evidence for stratification, including desmosome formation and microvilli development at the superficial cell layer. As the culture grew, these cells began to express cornea-specific 64 kD cytokeratins. In contrast to cultured normal corneal epithelial cells, this cell line had a good proliferative ability after a long-term storage in liquid nitrogen. CONCLUSIONS: Because this particular cell line shares properties consistent with normal corneal epithelial cells and is easy to handle in vitro, it may serve as a useful tool in corneal epithelial research.

Animals↗

[A midbrain arteriovenous malformation at quadrigeminal plate completely obliterated by embolization].

An eighteen year-old boy presented sudden loss of consciousness and tetraparesis. Radiological examinations revealed a ruptured midbrain arteriovenous malformation (AVM) at the right quadrigeminal plate. The patient recovered from symptoms by conservative treatment over 6 months with residual right hemisensory disturbance and mild diplopia during bilateral horizontal gaze. One year later, he was admitted to our institute for radical treatment of the AVM. On the angiography, the AVM was fed by two branches of the right long circumferential artery and a left paramedian penetrating artery of the posterior cerebral artery (PCA), and drained into the straight sinus via a dilated quadrigeminal vein. After much discussion on several strategies, endovascular surgery was chosen as a radical treatment. In the initial session, a medial branch of the right long circumferential artery was catheterized with Tracker-18, and embolized with 1.0 ml of ethylene vinyl alcohol copolymer (EVAL) without any deficits after negative provocative tests using Amytal and Xylocaine. Then, a lateral branch of the same artery was embolized with 0.8 ml of EVAL in the same way without any deficits. In the second session, catheterization into the left paramedian artery was difficult because of its small diameter and steep branching angle, and only a 3 mm hooked tip of Tracker-18 could be canulated into the feeding pedicle. Left oculomotor palsy was induced by provocative Xylocaine test. However, angiographic cure of the AVM was expected to be made possible by the occlusion of this pedicle, and the procedure was continued due to the request of the patient and his family.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Transcriptional regulation by a point mutant of adenovirus-2 E1a product lacking DNA binding activity.

The adenovirus E1a protein (E1A) regulates transcription through interaction with transcription factors bound to DNA, like cAMP response element BP1/ATF2, or through dissociating E2F transcription factor complex. However, it was also reported that E1A can bind to DNA (Chatterjee, P. K., Bruner, M., Flint, S. J., and Harter, M. L. (1988) EMBO J. 7, 835-841), and it is not clear whether DNA binding of E1A is involved in a part of the process of transcriptional regulation by E1A. In this paper, the small region of E1A that is responsible for DNA binding was identified and a point mutant lacking DNA binding activity was constructed. Analysis of deletion mutants of E1A proteins expressed in bacteria showed that a basic region between amino acids 201 and 216 of E1A is essential for DNA binding. Point mutation of arginines at amino acid numbers 205 and 206 to aspartic acids completely abolished the DNA binding activity of E1A. Using this mutant, the requirement of the E1A DNA binding for E1A-dependent transcriptional regulation was examined. trans-Activation of the adenovirus E4 promoter and trans-repression of the human c-erbB-2 promoter by this point mutant were examined by cotransfection experiments. Mutations of the E1A DNA-binding domain affected neither the E1A-induced trans-activation nor trans-repression at all. These results give complete proof that the DNA binding activity of E1A is not required for transcriptional regulation by E1A.

Adenovirus E1A Proteins↗

RNA editing of atp6 transcripts from male-sterile and normal cytoplasms of rapeseed (Brassica napus L.).

The complete cDNA sequence corresponding to the rapeseed atp6 gene transcript (coding for subunit 6 of F0-ATPase) has been determined by a method involving cDNA synthesis, using specific oligonucleotides as primers, followed by PCR amplification, cloning and sequencing of the amplification products. Only one modification, a C-to-U conversion, has been found when compared to the genomic mitochondrial DNA sequence. Comparison of the extent and frequency of RNA editing of the pol cytoplasmic male sterile (cms) atp6 transcript with those of normal atp6 transcript indicates that there is no variation between the editing status of the atp6 transcripts from pol cms and normal cytoplasms.

Amino Acid Sequence↗

A common trans-acting factor, Ad4-binding protein, to the promoters of steroidogenic P-450s.

Previous studies of bovine CYP11B1 gene regulation revealed six cis-acting elements, Ad1, Ad2, Ad3, Ad4, Ad5, and Ad6, in the 5' upstream region of the gene. Ad4 site was a positive transcription element in the stimulation by cAMP. Ad4-binding protein (Ad4BP) was purified from the nuclear extract of bovine adrenal cortex using affinity latex particles conjugated with polymerized Ad4 sequences. The molecular mass of the purified Ad4BP estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was approximately 53 kDa. To characterize the binding specificity of Ad4BP, oligonucleotides homologous to Ad4 sequence and AGGTCA containing sequences in the promoter regions of steroidogenic P-450s were synthesized and used for gel shift analyses as competitors. The competition experiments revealed that Ad4BP bound not only to (C/T)CAAGG(T/C)(C/T), which was originally identified as the Ad4 binding site, but also to (Pu)PuPuAGGTCA. All the steroidogenic P-450 genes examined had at least one Ad4BP binding sequence. Experiments with model sequences containing various nucleotide substitutions established that (C/T)CAAGG(T/C)CA is the strongest binding sequence for Ad4BP. The expression of Ad4BP was examined with adrenal cortex cells and several other steroidogenic and nonsteroidogenic cells. Only the steroidogenic cells, the granulosa cells of bovine ovary, and I-10 cells derived from mouse Leydig cells, expressed the binding activity to Ad4 site. The presence of Ad4 site as a common cis-acting element in the genes of all the steroidogenic P-450s and the steroidogenic tissue-specific expression of Ad4BP strongly suggests that Ad4BP is an indispensable transcription factor for the expression of all the steroidogenic P-450 genes.

Adrenal Cortex↗

Generation of microglial cell lines by transfection with simian virus 40 large T gene.

Microglial cells, which were isolated from a primary culture of neonatal rat brain, were transfected with temperature-sensitive simian virus 40 (SV40) large T gene by the calcium phosphate precipitation method. Four weeks after transfection, several colonies were generated, and cloned cells were characterized. One of the cloned cells (RBM129) proliferated actively at 37 degrees C and the dividing rate was significantly decreased at 40.5 degrees C. The expression of large T antigen was detected by western blotting in cells incubated at both 37 degrees C and 40.5 degrees C. The cell line showed high activity of non-specific esterase, isolectin B4 binding and phagocytosis. Also the cells were stained by ED 1 monoclonal antibody. These results indicate that these cells were derived from rat brain microglia, and immortalized by large T gene.

Animals↗

The gene for tRNA(Lys) is encoded in the rapeseed (Brassica napus L.) mitochondrial DNA.

The nucleotide sequence of the gene coding for tRNA(Lys) and its flanking regions from the rapeseed mitochondrial genome are presented and compared with other known tRNA(Lys) genes from plant mitochondria. This tRNA sequence can be folded into the standard cloverleaf structure model. Also, this tRNA sequence shows less similarity with its chloroplast counterparts and therefore appears to be 'native' mitochondrial tRNA.

Base Sequence↗

Different organization and altered transcription of the mitochondrial atp6 gene in the male-sterile cytoplasm of rapeseed (Brassica napus L.).

The Fo-ATPase subunit 6 gene (atp6) of rapeseed mitochondria has been isolated from both pol male-sterile and normal (fertile) cytoplasms in order to determine whether the rearrangements around the atp6 locus in pol male-sterile cytoplasm play a role in cytoplasmic male-sterility (cms). The pol cms and normal atp6 genes are identical and encode a 261-amino acid polypeptide. As a result of extensive rearrangement, a novel reading frame (pol-urf) was generated upstream of the atp6 gene only in pol cms mitochondria, which encoded 105 amino acids and might be co-transcribed with atp6. A 5'-portion of pol-urf shows sequence homology to the Oenothera ORFB gene associated with coxIII. A 5'-flanking region of the pol-urf also shows homology to that of ORF105 in Ogura cms radish mitochondria. These DNA rearrangements which give rise to pol-urf in the vicinity of the atp6 locus may be responsible for cms in rapeseed.

Amino Acid Sequence↗

Endovascular coil embolization of a recurrent giant internal carotid artery aneurysm via the posterior communicating artery after cervical carotid ligation: case report.

The case of a 29-year-old man with a giant fusiform aneurysm of the left internal carotid artery (ICA) is presented. The aneurysm, treated by cervical ICA ligation and extracranial-intracranial bypass, recurred 4 years later owing to recruitment of the posterior communicating artery (PCoA). Because of the previous bypass surgery a direct surgical approach was excluded. After an initial failure with balloon embolization, the aneurysm was embolized successfully with occlusive platinum microcoils through the microcatheter navigated into the aneurysm via the enlarged PCoA. Endovascular coil embolization may be useful in the treatment of cerebral aneurysms not amenable to direct surgery or balloon embolization.

Adult↗

Direct purification of multiple ATF/E4TF3 polypeptides from HeLa cell crude nuclear extracts using DNA affinity latex particles.

We developed a method using affinity latex particles to rapidly and efficiently purify DNA-binding proteins directly from crude cell extracts. The particles are composed of a styrene core and a polyglycidyl methacrylate surface, to which DNA oligomers were immobilized by means of epoxy groups. Multiple polypeptides were copurified, which bound to the ATF/E4TF3-binding site from crude nuclear extracts of HeLa cells, within a few hours. Affinity-purified polypeptides stimulated transcription in vitro from a promoter in which ATF/E4TF3-binding sites were present. At least eight polypeptides with molecular masses of 116, 80, 65, 60, 55, 47, 45, and 43 kDa were copurified. About 2 micrograms of the 43-kDa protein was purified directly from 8 mg of crude nuclear extracts. All the polypeptides directly bound to the same DNA sequence and were thought to form a family. The results indicated that the particles are useful for quickly purifying various DNA-binding proteins directly from crude cell extracts.

Activating Transcription Factors↗

Blood pressure changes following extracorporeal shock wave lithotripsy for urolithiasis.

Hypertension after extracorporeal shock wave lithotripsy (ESWL) has been a controversial subject. Changes in blood pressure were studied in 262 patients (mean age 47.8 years) 18.6 months after ESWL. According to World Health Organization criteria the number of patients who showed a decrease exceeded those who showed an increase in blood pressure. The patients who have been on antihypertensive therapy showed a significantly greater decrease in blood pressure than those without medication. Of 192 normotensive patients diastolic pressure increased 1.2 mm. Hg and 2 (1.0%) had hypertension 18.4 months after ESWL. Annualized increase in diastolic pressure and new onset of hypertension were calculated to be 0.78 mm. Hg and 0.65%, respectively. Significant elevation of diastolic pressure was noted in the patients who received a larger number of shock waves. Blood pressure should be carefully followed after ESWL especially in patients who have been treated by a greater number of shock waves.

Adult↗