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Biomedical subjects

I Suzuki

Publications and source records attributed to I Suzuki.

At least 19 recordsLinked to original sources
PubMed1995

Polymorphism and utilization of human VH Genes.

The human VH germline repertoire comprises approximately 100 elements, which can be grouped into seven families based on nucleotide sequence similarity. Members of different families are interspersed throughout the complex, with limited sets of alleles identified for most loci. Linkage disequilibrium between most elements is weak. Variation within the population can be attributed to differences in nucleotide sequence between allelic genes as well as to differences in the number of genes present. Gene number per haplotype varies as a result of the common occurrence of insertion/deletion polymorphisms, which may be small, involving a single element, or may be extensive, involving four or five elements. In some cases, such polymorphisms may involve duplication of a functional VH gene segment on some haplotypes and deletion of the gene on others. The resulting variation in germline composition of the VH locus may have profound effects on VH gene utilization.

Alleles↗
PubMed1995

Comparison of the reactivity of tetradecenoic acids, a triacsin, and unsaturated oximes with four purified Saccharomyces cerevisiae fatty acid activation proteins.

Saccharomyces cerevisiae contains at least five acyl-CoA synthetases (fatty acid activation proteins, or Faaps). Four FAA genes have been recovered to date. Recent genetic studies indicate that Faa1p and Faa4p are involved in the activation of imported fatty acids, while Faa2p activates endogenous pools of fatty acids. We have now purified Faa4p from S. cerevisiae and compared its fatty acid substrate specificity in vitro with the specificities of purified Faa1p, Faa2p, and Faa3p. Among C8-C18 saturated fatty acids, Faa4p and Faa1p both prefer C14:0. Surveys of C14 fatty acids with single cis-double bonds at C2-C12 indicated that Faa4p and Faa1p prefer Z9-tetradecenoic acid, although Faa4p's preference is much greater and also evident in C16 and C18 fatty acids. Faa4p's selectivity for fatty acids with a C9-C10 cis-double bond is a feature it shares with Faa3p and is notable since in yeast Ole1p, a microsomal cis-delta 9 desaturase, accounts for de novo production of monoenoic acyl-CoAs from saturated acyl-CoA substrates. Faa4p has no detectable acyl-CoA synthetase activity when incubated with tetradecenoic acids having a trans-double bond at C2-3, C4-5, C5-6, C6-7, C7-8, or C9-10. Faa3p can only use E9-tetradecenoic acid as a substrate, while E4-, E6- and E9-tetradecenoic acids can be used by Faa1p and Faa2p. E2-tetradecenoic acid is an Faap inhibitor, with Faa2p exhibiting the greatest sensitivity (IC50 = 2.6 +/- 0.2 microM). Triacsin C (1-hydroxy-3-(E,E,E,2',4',7'- undecatrienylidine)-1,2,3-triazene) has trans-double bonds at positions that correspond to those in E2-, E5-, and E7-tetradecenoic acids. This compound is a potent inhibitor of Faa2p (Ki = 15 +/- 1 nM; competitive with fatty acid), less potent against Faa4p (Ki = 2 microM), and not active against Faa1p or Faa3p (IC50 > 500 microM). Analysis of an n-tetradecanal plus a series of oximes (tridecanal oxime, 1-azadeca-1,3,5-trienol, and 1-azaundeca-1,3,5-trienol) indicated that the combination of an azenol moiety (R-CH = N-OH) plus adjacent unsaturation are critical for triacsin C's selective inhibition of Faa2p. Triacsin C and oxime derivatives appear to be very useful for defining differences in molecular recognition among S. cerevisiae acyl-CoA synthetases. The > 25,000-fold range in the inhibitory effects of triacsin C on these four Faaps suggests that it may be possible to develop other selective inhibitors of eukaryotic acyl-CoA synthetases.

Base Sequence↗
PubMed1995

Representation of rearranged VH gene segments in the human adult antibody repertoire.

The heavy chain variable region composition of the human adult Ab repertoire is poorly defined, but recent evidence suggests that peripheral blood B cells may express a nonstochastic assortment of VH genes. In this study, the contribution of individual VH gene segments to the human Ab repertoire has been assessed. As a measure of VH gene utilization, the frequency of occurrence of eight individual VH3 gene segments contained in rearrangements was assessed in the peripheral blood B cells of two adult subjects. In addition, the frequency of occurrence of rearrangements containing nine individual VH4 gene segments was analyzed in one of the subjects. More than 2500 independent rearrangements were analyzed. For controls, amplifications and subsequent identification of nonrearranged VH3 and VH4 genes from the same individuals were also performed. The results of this germ-line analysis indicated that approximately 25 VH3 gene segments and nine VH4 gene segments could be amplified quantitatively. However, usage of elements was not uniform; one VH3 element, V3-23, and one VH4 element, V4-34, were represented among rearrangements more frequently than were other members of their respective families. This pattern of VH utilization was apparent in B cells isolated from the same subject after an 8-mo interval, indicating the relative stability of the repertoire over time. These results indicate that the adult human Ab repertoire is dominated by a few VH genes demonstrating a pattern of nonrandom utilization that could involve preferential rearrangement and/or receptor-dependent selection.

Adult↗
PubMed1995

Mitogenic and melanogenic stimulation of normal human melanocytes by melanotropic peptides.

The significance of melanotropic hormones as physiologic regulators of cutaneous pigmentation in humans is still controversial. Until recently, no direct effect for melanotropins could be demonstrated on human melanocytes. Here we present conclusive evidence that alpha-melanotropin (alpha-melanocyte-stimulating hormone, alpha-MSH) and the related hormone corticotropin (adrenocorticotropic hormone, ACTH) stimulate the proliferation and melanogenesis of human melanocytes maintained in culture in a growth medium lacking any AMP inducer. The minimal effective dose of either hormone is 0.1 nM. In time-course experiments, the increase in cell number and tyrosinase activity became evident after one treatment of the melanocytes with 100 nM alpha-MSH for 48 hr. The mitogenic effect gradually increased to 50-270% above control, depending on the individual melanocyte strain, with continuous treatment with 100 nM alpha-MSH for 8 days, whereas the melanogenic effect became maximal (70-450% increase above control) after 4 days of treatment. Western blot analysis of tyrosinase and the tyrosinase-related proteins TRP-1 and TRP-2 revealed that alpha-MSH increased the expression of those three melanogenic proteins. This was not accompanied by any change in their mRNA levels after brief (1.5-24 hr) or prolonged (6 days) treatment with 100 nM alpha-MSH, suggesting that the increased expression of these melanogenic proteins was due to posttranscriptional events. These results demonstrate both mitogenic and melanogenic effects of alpha-MSH and ACTH on human melanocytes. That both hormones are effective at subnanomolar concentrations, combined with the presence of melanotropin receptors on human melanocytes, strongly suggests that these melanotropins play a physiologic role in regulating human cutaneous pigmentation.

Adrenocorticotropic Hormone↗
PubMed1995

Bactericidal effect of rat cystatin S on an oral bacterium Porphyromonas gingivalis.

We tested antibacterial and antiviral activities of rat cystatin S, a cysteine proteinase inhibitor, belonging to the family 2 cystatins against 18 different bacterial species and poliovirus type 1 (Sabin). Rat cystatin S specifically inhibited the growth of a human oral anaerobic bacterium Porphyromonas gingivalis due to a bactericidal effect.

Amino Acid Sequence↗
PubMed1995

Computed tomographic evaluation of lymph node metastasis in head and neck carcinomas.

A retrospective study of 53 patients was undertaken to evaluate the efficacy of computer tomography (CT) in the detection of nodal metastases from carcinomas of the head and neck. The CT findings of 53 patients with head and neck carcinomas who underwent a total of 57 neck dissections were compared with the findings of physical examination (PE) and histopathological examination. Using node size larger than 10 mm in the short-axis diameter or the presence of central lucency as the criteria of nodal metastasis CT scanning staged correctly 52 of 57 necks, providing an accuracy of 91%, a sensitivity of 86% and a specificity of 100% in the detection of nodal metastases. There was agreement of PE findings with histology in 43 (74%) of 57 necks, with a sensitivity of 97% and a specificity of 38%, respectively. Because CT scanning was superior to PE in the pre-operative staging of head and neck carcinomas, it should be used for pre-operative evaluation of metastatic neck disease.

Carcinoma, Squamous Cell↗
PubMed1995

CYP1A1 and CYP2E1 polymorphism and lung cancer, case-control study in Rio de Janeiro, Brazil.

Msp I polymorphism and exon 7 Ile-Val polymorphism of CYP1A1, and Rsa I polymorphism of CYP2E1 were studied in lung cancer patients and controls in Rio de Janeiro, Brazil. Of the three polymorphisms studied, only the exon 7 polymorphism of CYP1A1 (Val-containing genotypes) had a distribution which was statistically significant in the patients and controls. The contribution of Val containing genotypes of CYP1A1 exon 7 was greater in the subpopulation of squamous cell carcinoma patients with a lower life-time smoking consumption (OR, 2.92 vs 1.97). This association is consistent with the previous findings by Kawajiri et al. and the first observation of the positive association of this locus with lung cancer in a Western population (Kawajiri K, Nakachi K, Imai K, Yoshii A, Shimada N, Watanabe J. FEBS Let 1990; 263, 131-133). Furthermore, together with the lack of association of Msp I polymorphism in the non-coding region of CYP1A1, the locus truly responsible for lung cancer risk among pleural polymorphisms of CYP1A1 appeared to be exon 7 Ile-Val polymorphism. In the future, investigations of multiple markers in different ethnic populations may reveal cancer risk markers common to all mankind.

Base Sequence↗
PubMed1995

Identification and characterization of two nitrogen-regulated genes of the cyanobacterium Synechococcus sp. strain PCC7942 required for maximum efficiency of nitrogen assimilation.

Two nitrogen-regulated genes were found in the genomic DNA region upstream of the nirA operon involved in uptake and utilization of nitrate in Synechococcus sp. strain PCC7942. The two genes (nirB and ntcB) are transcribed divergently from nirA and encode proteins of 349 and 309 amino acid residues, respectively. The levels of nirB and ntcB transcripts were low in cells growing on ammonium and increased upon transfer of ammonium-grown cells to nitrate-containing medium. The deduced NirB protein sequence has no similarities to other known proteins, whereas the deduced NtcB protein sequence is homologous to bacterial transcriptional activators of the LysR family. Defined mutants constructed by interrupting nirB or ntcB with a drug resistance marker grew as fast as the wild-type strain on ammonium but grew slower than the wild-type strain on nitrate or nitrite. The nirB mutant had higher activities of nitrate reductase, glutamine synthetase, and glutamate synthase than the wild-type strain, but its nitrite reductase activity was 40% of the wild-type levels. The mutant excreted nitrite into the medium during growth on nitrate, showing that nitrite reductase limits nitrate assimilation. These findings suggested that nirB is required for expression of maximum nitrite reductase activity. When grown on ammonium, the nirB mutant grew normally but cultures of the ntcB mutant still showed a yellowish-green color typical of nitrogen-limited cells. NtcB seems to regulate utilization of fixed nitrogen by controlling the expression of a certain gene(s) involved in nitrogen metabolism.

Amino Acid Sequence↗
PubMed1995

A novel nitrite reductase gene from the cyanobacterium Plectonema boryanum.

The gene (nirA) for nitrite reductase was cloned from the nonheterocystous, filamentous cyanobacterium Plectonema boryanum. The predicted protein consists of 654 amino acids and has a calculated molecular weight of 72,135. The deduced amino acid sequence from positions 1 to 511 is strongly similar to the entire sequence of the ferredoxin-dependent nitrite reductases from other phototrophs, while the remainder of the protein is unique to the Plectonema nitrite reductase. The C-terminal portion of the protein (amino acids 584 to 654) is 30 to 35% identical to [2Fe-2S] ferredoxins from higher plants and cyanobacteria, with all of the four Cys residues involved in binding of the [2Fe-2S] cluster in the ferredoxins being conserved. Immunoblotting analysis of the extracts of P. boryanum cells showed that the NirA polypeptide has an apparent molecular mass of 75 kDa. An insertional mutant of nirA lacked the 75-kDa polypeptide, had no nitrite reductase activity, and failed to grow on nitrate and nitrite, indicating that the novel nirA is the sole nitrite reductase gene in P. boryanum and that the NirA polypeptide with the ferredoxin-like domain is the apoprotein of the functional nitrite reductase. As in Synechococcus sp. strain PCC7942, nirA is the first gene of a large transcription unit (> 7 kb in size) and is repressed by ammonium and derepressed simply by deprivation of ammonium from the medium. The development of nitrite reductase activity was, however, found to require the presence of nitrate in the medium.

Amino Acid Sequence↗
PubMed1995

En bloc petrosectomy using a Gigli saw for petroclival lesions. Technical note.

The authors report a new technique for en bloc petrosectomy using a Gigli saw as an alternative to drilling the petrous bone in the combined supra- and infratentorial approach or the transpetrosal-transtentorial approach. It is simple and easy and avoids postoperative cosmetic deformity. This technique has been performed in 11 petroclival lesions without injuring the semicircular canals, the cochlea, or the facial nerve.

Craniotomy↗
PubMed1995

Degradation of cystathionine gamma-lyase in rat liver lysosomes: effect of leupeptin treatment.

Highly purified lysosomes from the livers of normal and leupeptin-treated rats were subjected to immunoblot analysis, using antibodies against rat liver cystathionine gamma-lyase. Normal lysosomes showed small amount of single band at about 40 kDa, whereas the leupeptin-treated lysosomes showed large amounts of a major band at about 40 kDa and a minor band at about 35 kDa. These observations suggest that cystathionine gamma-lyase is sequestered into lysosomes at the original subunit molecular weight and is degraded in the lysosome by way of the sequential formation of an intermediate with distinct molecular weight.

Animals↗
PubMed1995

Changes in cystathionine gamma-lyase in various regions of rat brain during development.

Developmental changes in the activities of cystathionine beta-synthase and cystathionine gamma-lyase were measured in six regions of rat brain. On day-1, no differences were observed in the activities of cystathionine beta-synthase and cystathionine gamma-lyase among these regions, the values being about 40 nmol/h/mg protein, and 3 nmol/h/mg protein, respectively. Cystathionine beta-synthase activity increased gradually during development at almost the same rate in each region, reaching the adult level at week-4 (about 4-fold). Cystathionine gamma-lyase activity also increased during development, reaching adult level at week-2. But, the increase of enzyme activity in the cerebellum (about 1.8-fold) was clearly lower than that in the other regions (about 4-fold). Cystathionine gamma-lyase content in the various regions of week-3 rat brain estimated by immunoblotting was consistent with the enzyme activity, and the enzyme level in the cerebellum was lower than that in the other regions. Cystathionine content of cerebellum in week-3 increased rapidly during development, and was about five-fold more than that on day-1. However, cystathionine content in the other regions did not change during development. These findings indicated that at least one reason of the high content of cystathionine in the 3 weeks rat cerebellum was due to the low level of cystathionine gamma-lyase.

Animals↗
PubMed1995

[A benign clear cell tumor of the lung that grew gradually over five years].

A 38-year-old man was found to have an abnormal shadow in his chest X-ray film during a general medical examination. A nodule with a homogeneous density and a clear margin was seen in the upper lobe of the right lung. Since this shadow gradually enlarged during a five-year follow-up period, he was admitted to our hospital. Chest contrast and dynamic CT scans and aortography showed characteristics of a benign tumor with somewhat rich vascularity. The doubling time of this tumor was about 430 days. Transbronchial brushing for cytologic study and a transbronchial biopsy showed no malignancy. However, the tumor was surgically resected because of its gradual growth over the five years. The resected tumor was histologically diagnosed as a benign clear cell tumor of the lung. This disease was first described by Leibow and Castleman in 1963, as a benign pulmonary tumor similar to metastatic renal cell carcinoma. This disease is extremely rare and only 61 cases have been reported: twenty cases, including the present case, in Japan and 41 in other countries.

Adenocarcinoma, Clear Cell↗
PubMed1995

Pancreatic arteriovenous malformation involving adjacent duodenum in a patient with gastrointestinal bleeding.

Gastrointestinal bleeding caused by arteriovenous malformation (AVM) of the pancreas is extremely rare. A 56-yr-old man with AVM of the head of the pancreas who was presented with recurrent episode of melena is described herein. The preoperative diagnosis was confirmed by angiographic study, and he was successfully treated with pancreatoduodenectomy. Histological examination of the resected specimen revealed pancreatic AVM involving the adjacent duodenal wall.

Arteriovenous Malformations↗
PubMed1995

Evaluation of long-term results of Caroli's disease: 21 years' observation of a family with autosomal "dominant" inheritance, and review of the literature.

A 5-year-old girl underwent laparotomy in 1972 because of hepatomegaly and mottled radiopacities shown by cholangiography. Polycystic segmental dilatation of the intrahepatic bile ducts, typical of Caroli's disease, was found. Thereafter she remained in good health for over 21 years with careful medical management. In 1972 mottled radiopacities of the hepatic parenchyma were also demonstrated by cholangiography in her 9-year-old brother, who, however, remained asymptomatic until hematemesis due to esophageal varices suddenly occurred in 1993. At the time of the pre-operative evaluation for esophageal transection, his condition was definitively diagnosed as Caroli's disease. Their father was in good health, but in 1993 was shown by CT to have the same disease. The mode of inheritance is likely to be autosomal dominant, although Caroli's disease or congenital hepatic fibrosis is generally considered autosomal recessive (McKusick number 263200) (1). If we had not examined the father, this particular family would have been accepted as an example of autosomal recessive inheritance. We suggest that further family studies are needed to exclude the autosomal dominant mode of inheritance, and that at least some of the recessive cases in the literature are, in fact, autosomal dominant. Well-documented cases of "classical" Caroli's disease in the literature were reviewed with special reference to the long-term results. In addition, an international questionnaire aimed at establishing the further clinical course of the patient was sent to authors who reported cases after 1968.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

[Neural control of tracheal smooth muscle during cough].

Contraction of tracheal smooth muscle during mechanically induced coughing was studied in dogs. Recordings of smooth muscle tension were obtained from the cervical trachea, which is not influenced by intrathoracic pressure. We observed that during breathing at rest, tracheal smooth muscle contracts and relaxes in synchrony with phrenic nerve activity. When cough occurs, the tracheal smooth muscle contracts continuously and tonically with no rhythmic correlation to phrenic nerve activity. Sometimes the contraction starts before the phrenic nerve activity increases. A neuromuscular blocking agent caused a significant decrease in phrenic nerve activity in response to mechanical stimulation. The correlation between phrenic nerve activity and tracheal smooth muscle tension during normal breathing was also observed after afferent inputs from pulmonary mechanoreceptors were interrupted. During coughing, however, this correlation was lost. From these results we conclude that the neural control of tracheal smooth muscle is at least partially independent of phrenic nerve activity during coughing. Because coughing was attenuated by neuromuscular blocking agents, we speculate that there is a positive feedback mechanism from receptors in the chest wall or airway, which increases the magnitude of coughing.

Animals↗