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Biomedical subjects

Y Kai

Publications and source records attributed to Y Kai.

At least 91 records · Page 5Linked to original sources

A Case of Breast Cancer Coexisting with Florid Papillomatosis of the Nipple.

We report a 47 year-old woman with a unique breast cancer coexisting with florid papillomatosis (FP) of the left nipple. The diseased nipple was enlarged and reddened. There was an area of erosion on the surface. Incisional biopsy revealed FP of the nipple. Under the nipple, there was an elastic hard tumor with an unclear border and irregular surface. Aspiration biopsy cytology of the tumor revealed carcinoma. Modified radical mastectomy was performed. Histological examination showed that the superior portion of the tumor was FP, and most of the tumor in and under the nipple was breast cancer. To the best of our knowledge, only 16 cases of FP of the nipple have been reported in the Japanese literature. FP of the nipple coexisting with carcinoma in the same nipple has never been reported. This is thought to be the first case in Japan of mammary carcinoma coexisting with FP in the same nipple.

Journal Article↗

Structure of azurin I from the denitrifying bacterium Alcaligenes xylosoxidans NCIMB 11015 at 2.45 A resolution.

Azurin I from Alcaligenes xylosoxidans NCIMB 11015 (AzN-I) was crystallized by using PEG 4000 as a precipitant. The crystals belong to the monoclinic crystal system and have a space group C2 with the unit-cell parameters of a = 130.67, b = 54.26, c = 74.55 A, and beta = 95.99 degrees. The structure of AzN-I has been solved by the molecular replacement method. Azurin II from the same bacterium (AzN-II) was chosen as the initial structural model. The final crystallographic R value is 17.3% and free R value is 23.6% for 10958 reflections at a resolution of 2.45 A. The root-mean-square deviations for main-chain atoms range between 0.19 and 0.26 A among the four independent molecules in the asymmetric unit. The Cu atom is coordinated to Ndelta of His46 and His117 at 2.0 (1) and 1.9 (1) A, and to Sgamma of Cys112 at 2.2 (1) A, while the carbonyl O atom of Gly45 and Sdelta of Met121 coordinate axially to Cu atom at 2.5 (1) and 3.1 (1) A, respectively. The Cu-N and Cu-S distances of AzN-I are quite similar to those of AzN-II, however, the Cu-SO (Gly45) bond length in AzN-I is 0.25 A shorter than the counterpart in AzN-II. The results have been used to discuss the differences in the spectra of these two proteins.

Alcaligenes↗

A novel mode of target recognition suggested by the 2.0 A structure of holo S100B from bovine brain.

BACKGROUND: S100B, a small acidic calcium-binding protein, is a member of the S100 protein family and is a multifunctional protein capable of binding several target molecules, such as cytoskeletal proteins and protein kinases, in a calcium-dependent manner. S100B is a homodimer of S100 beta subunits (beta beta) with a total of four calcium-binding motifs called EF hands. S100B is found abundantly in nervous tissue and has been implicated in Alzheimer's disease and Down's syndrome. Structural analysis of S100B in the calcium-bound state is required to gain a better understanding of the conformational changes that occur to S100B upon calcium binding and to elucidate the mode of recognition between S100B and its target molecules. RESULTS: We have determined the three-dimensional structure of holo S100B from bovine brain at 2.0 A resolution by X-ray diffraction. The dimeric S100B molecule is formed by non-covalent interactions between large hydrophobic surfaces on both S100 beta subunits. There are two EF-hand motifs per S100 beta subunit, each of which binds one calcium ion. We observe, in the calcium-bound structure, dramatic changes in the conformation of the terminal helices, from the compact structure in the apo form to a more extended form upon binding calcium. Following these changes, an exposed hydrophobic core, surrounded by many negatively charged residues, is revealed. Cys84 is positioned at an exposed surface of S100B, surrounded by hydrophobic residues, and could form a disulfide bond to tau protein, one of the known target molecules thought to interact with S100B in this way. CONCLUSIONS: The molecular structure of holo S100B suggests a novel mode of target recognition for the S100 family of calcium-binding proteins. Upon calcium binding, dramatic changes occur in the terminal helices of S100B, revealing a large hydrophobic surface, not observed in the apo form. It is through hydrophobic interactions and possibly a Cys84-mediated disulfide bond that S100B is thought to bind its target molecules.

Amino Acid Sequence↗

Type 1 Cu structure of blue nitrite reductase from Alcaligenes xylosoxidans GIFU 1051 at 2.05 A resolution: comparison of blue and green nitrite reductases.

The crystal structure of the blue nitrite reductase from Alcaligenes xylosoxidans GIFU 1051 (AxgNIR) has been determined at 2.05 A resolution. AxgNIR contains both type 1 and 2 Cu sites, the geometry of the former being distorted tetrahedral. The superpositioning of the type 1 Cu sites in the blue enzyme and a green nitrite reductase revealed that the orientation of the Met150 side chain differed. The deviation of the Sdelta(Met150) atom from the axial position of the NNS plane formed by two Ndelta(His95 and His145) and one Sgamma(Cys136) atom caused the difference in the colors of the enzymes, i.e. blue and green.

Alcaligenes↗

Primary malignant lymphoma of the brain in childhood.

A 5-year-old boy presented with a 1-year history of frontal headache and nausea. Neurological examination showed left abducens nerve palsy, left facial nerve palsy, Bruns' nystagmus, and wide-based gait. Neuroimaging demonstrated a lesion with moderate linear enhancement in the left cerebellar hemisphere. He underwent stereotactic needle biopsy. The histological diagnosis was well-differentiated small lymphocytic type of malignant lymphoma. Following the biopsy, the patient underwent radiotherapy (whole brain 30 Gy, local 20 Gy). He has been in good condition for more than 5 years. The long-term survival is attributable to the absence of aggressiveness and the good response to radiation of this subtype of malignant lymphoma.

Brain Neoplasms↗

Effect of emeriamine, an inhibitor of fatty acid oxidation, on metabolic fate of a geometrical isomer of linoleic acid in perfused rat liver.

To estimate the relative significance of exogenous vs. endogenous fatty acids in increasing hepatic triacylglycerol secretion following an inhibition of fatty acid oxidation by emeriamine, livers from 2-d-fasting rats were perfused with or without an inhibitor in the presence of a geometrical isomer of linoleate (linolelaidic acid, trans,trans-9,12-octadecadienoic acid). Emeriamine added to the perfusion medium at 2 h of the recirculating perfusion period caused immediate and complete cessation of ketone body production while it increased triacylglycerol and cholesterol secretion by the liver without affecting uptake of exogenous linolelaidic acid. The increase in the triacylglycerol secretion by emeriamine was accompanied by a marked increase in the proportion of linolelaidic acid in this lipid molecule in the perfusate and in the liver. The calculated amounts of exogenous linolelaidate, compared with those of endogenous fatty acids in the secretory triacylglycerol, suggested that the former compared with the latter contributes more to the drug-mediated increase in triacylglycerol secretion. This drug caused a marked reduction of mitochondrial carnitine palmitoyltransferase activity in perfused liver. These results suggest that a blockade of fatty acid oxidation by emeriamine, through an inhibition of carnitine palmitoyltransferase, diverts predominantly the exogenous free fatty acids from oxidation to the esterification pathway and subsequently stimulates the synthesis and secretion of triacylglycerol-rich lipoproteins.

3-Hydroxybutyric Acid↗

[Clinical study on chlormadinone acetate alone followed by combination with LH-RH analogue for prostatic cancer: effects on lipid metabolism].

Twenty-four previously untreated patients with a diagnosis of prostatic cancer were treated with chlormadinone acetate (CMA) alone (100 mg/day) for 4 weeks, and luteinizing hormone-releasing hormone analogue (LH-RHa) was added for the next 24 weeks. Marked decreases in blood LH, testosterone (T), prostate specific antigen (PSA), gamma-seminoprotein (gamma-Sm), and prostatic acid phosphatase (PAP) were observed after a single dose of CMA. T levels were significantly increased 3 days after the initial dose of LH-RHa, and did not return to the pretreatment level. There were no significant increases in any of the markers, nor were there any flare-up cases. Triglyceride levels, which were slightly elevated before the start of treatment, were significantly decreased 24 weeks after the completion of combined therapy. PSA was evaluated as partial response (PR) or better in 86.7% of the patients. Overall evaluation showed PR or better in 75.0% of the patients. These findings suggest that prior administration of CMA followed by combined administration with LH-RHa is useful in the treatment of prostatic cancer. No negative effects on lipid metabolism were observed at any time during the treatment period.

Aged↗

[A case of untreatable progressive bladder carcinoma effectively treated by single administration of tegafur and uracil].

Bloody urine was grossly observed and multinodular shadow confirmed in both lungs of an 81-year-old male, who had been referred to our department. The diagnosis was bladder cancer (TCC, G3, T4N3M1) from detailed examination. With his advanced age and lowered ADL, the family did not wish for aggressive treatment, so no combination multidrug chemotherapy was attempted. Instead he was given 300 mg/day UFT per os. After 4 weeks administration, the metastatic focus decreased and tended to contract; at the same time gross observation revealed no more bloody urine. Moreover, following 7 weeks of administration, the bladder tumor disappeared, the lung metastatic focus showed overall shrinkage of over 50%, the lymph node metastasis also was more than 50% less, and the case was considered to be PR. The literature reveals UFT was efficacious in only 2 other cases of progressive bladder carcinoma. Since UFT has fewer complications, such as myelosuppression, among antitumor agent, it is considered worth trying in cases where intensive treatment is not feasible.

Aged↗

In vivo determination of replication origins of human mitochondrial DNA by ligation-mediated polymerase chain reaction.

A large part of replication is aborted in human mitochondria, the result being a D-loop. As few attempts have been made to distinguish free 5' ends of true replicate from those of abortive ones, we examined the 5' ends of true replicate of human mitochondrial DNA at one nucleotide resolution in vivo by making use of ligation-mediated polymerase chain reaction. The distribution and relative amounts of origins of the true replicate are exactly the same as those of total newly synthesized heavy strands, which means that the abortion of replication is independent of 5' ends. Treatment of DNA with RNase H frees 5' ends on both heavy and light strands. This is the first in vivo evidence for covalently attached primer RNA to nascent strand in human mitochondrial DNA.

DNA Replication↗

Crystallization and preliminary X-ray studies of azurin-I and azurin-II from denitrifying bacterium Alcaligenes xylosoxidans GIFU 1051.

Two distinct azurins named azurin-I and azurin-II were isolated from Alcaligenes xylosoxidans GIFU 1051 (AzG-I and AzG-II). They have been purified and crystallized. The crystals of AzG-I belong to the monoclinic crystal system, space group C2, unit-cell parameters a = 130.6, b = 54.4, c = 74.7 A, beta = 96.1 degrees. The crystals of AzG-II belong to the tetragonal crystal system, space group P4(1)22 or P4(3)22, unit-cell parameters a = b = 52.6, c = 100.7 A. Both crystals diffract up to 2.0 A resolution and are suitable for X-ray crystallographic studies.

Journal Article↗

The content of intracellular mitochondrial DNA is decreased by 1-methyl-4-phenylpyridinium ion (MPP+).

1-Methyl-4-phenylpyridinium ion (MPP+), an oxidative metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is considered to be directly responsible for MPTP-induced Parkinson's disease-like symptoms by inhibiting NADH-ubiquinone oxidoreductase (complex I) in the mitochondrial respiratory chain. Here we demonstrate that 25 microM MPP+ decreases the content of mitochondrial DNA to about one-third in HeLa S3 cells. On the contrary, 0.1 microM rotenone, which inhibits complex I to the same extent as 25 microM MPP+ in the cells, increases the content of mitochondrial DNA about 2-fold. Hence, the effect of MPP+ on mitochondrial DNA is not mediated by the inhibition of complex I. To examine the replication state of mitochondrial DNA, we measured the amount of nascent strands of mitochondrial DNA. The amount is decreased by MPP+ but increased by rotenone, suggesting that the replication of mitochondrial DNA is inhibited by MPP+. Because the proper amount of mitochondrial DNA is essential to maintain components of the respiratory chain, the decrease of mitochondrial DNA may play a role in the progression of MPTP-induced Parkinson's disease-like symptoms caused by the mitochondrial respiratory failure.

1-Methyl-4-phenylpyridinium↗

Crystallization and preliminary X-ray studies of plastocyanin from Silene expressed in E. coli.

Plastocyanin from Silene (SilPc) expressed in E. coli has been crystallized in a form suitable for X-ray diffraction analysis by a macroseeding method using ammonium sulfate as a precipitant in acetate buffer (pH = 5.5). These crystals belong to the trigonal space group P3(1)21 or P3(2)21 with lattice parameters a = b = 76.6, c = 65.5 A, indicating an asymmetric unit containing two plastocyanin molecules. The crystals diffracted to at least 2.0 A.

Journal Article↗

Glucoregulatory disorders in school refusal students.

OBJECTIVES: Our previous studies demonstrated autonomic nervous system disorders and cerebral blood hypoperfusion in school refusal students with underlying emotional distress due to fear or anxiety associated with school attendance. Because severe stress is known to affect glucoregulatory metabolism, this study used the oral glucose tolerance test (OGTT) to measure glucose metabolism in school refusal students. DESIGN: A three-hour OGTT was performed. In preparation for the test, students fasted overnight. After a fasting blood sample was drawn, students were given solutions containing a predetermined amount of glucose based on their body weight (1.75 g/kg to a maximum 75 g). After glucose ingestion, blood samples were drawn at 30, 60, 90, 120, 150, and 180 mm to measure blood glucose (BG), immunoreactive insulin (IRI), pancreatic glucagon (IRG) and growth hormone (GH) levels. BG levels, IRI response, cumulative BG (sigma BG), cumulative IRI (sigma IRI), insulin/glucose ratio (delta IRI/delta BG), and insulinogenic index (sigma IRI/sigma BG) were then compared to previously reported normal control data. As an index of emotional difficulties, the self-rating depressive scale (SDS) was carried out. PATIENTS: Eighty-one school refusal students (40 males and 41 females), 11-19 years of age (14.8 +/- 2.1), were studied. Their school refusal periods ranged from one month to eight years. All students were within -15 to +20% (-0.04 +/- 8.6) of ideal body weight. MEASUREMENTS: BG levels were determined using a glucose oxidase reaction method. Serum hormones were measured by radioimmunoassay. RESULTS: BG levels at all OGTT time intervals and sigma BG were significantly higher in school refusal students than the normal control data (sigma BG: 39.5 +/- 4.4 vs 33.3 +/- 3.4 mmol/l P < 0.001). Although the insulin response was abnormally low relative to the prevailing hyperglycaemia (sigma IRI/ sigma BG: subjects vs control = 232 +/- 129 vs 375 +/- 271, P < 0.01), normal beta cell secretory ability was speculated (sigma IRI: subjects vs controls = 2805 +/- 1274 vs 2523 +/- 1219 pmol/l). This suggests a relative suppression of insulin secretion. A paradoxical increase of GH was observed in 19 students after glucose ingestion. CONCLUSIONS: Glucoregulatory disorders observed in school refusal students may be caused by emotional distress. Multiple factors including autonomic nervous system disorders, derangement of neuropeptides in the hypothalamus, and hormonal imbalances may also affect glucoregulatory metabolism, predisposing these students to hyperglycaemia. We speculate that the glucoregulatory system compensates for decreased blood flow to the brain by increasing blood glucose concentrations, thereby providing sufficient glucose as the primary energy source used during normal brain metabolism.

Adolescent↗

Structure of the zinc endoprotease from Streptomyces caespitosus.

A zinc endoprotease produced by Streptomyces caespitosus (ScNP) specifically hydrolyzes the peptide bond at the imino side of aromatic residues and is the smallest protease found to date. Although ScNP carries the zinc-binding sequence HEXXH, its primary structure of 132 amino acid residues differs from those of other known zinc metalloendoproteases. X-ray structural analysis of ScNP at 1.6 A resolution revealed that despite a lack of sequence homology, the common topological feature of main-chain folding and a beta-turn containing methionine, which is a feature of the zinc metalloendoprotease superfamily of metzincins, is conserved in ScNP. The zinc atom of ScNP is tetrahedrally ligated by the two histidines in the HEXXH sequence, an aspartate residue and a water molecule. Thus, ScNP represents a novel subfamily of metzincins with a HEXXHXXGXXD zinc-binding sequence. A plausible substrate recognition pocket to which aromatic residues bind is located near the catalytic zinc ion.

Amino Acid Sequence↗

Cerebellar mutism after posterior fossa surgery--two case reports.

Two adults (aged 71 and 74 years) developed cerebellar mutism after posterior fossa surgery for a mass lesion in the superior cerebellar hemisphere or upper vermis. Histological examination showed one was a hemangioblastoma, the other a metastatic brain tumor. The tumors were totally removed via the occipital transtentorial approach. Both patients developed mutism on the 2nd postoperative day, which persisted for 3-4 weeks and was followed within 2-4 months by cerebellar dysarthria. Thereafter, their condition improved. Transient cerebellar mutism usually occurs in pediatric patients after the removal of a mass lesion in the upper vermis. Cerebellar mutism in adults is rare. The predominance of cerebellar mutism in children may be attributable to the predilection for vermian tumor and their tendency to experience personality and behavioral changes after posterior fossa surgery.

Aged↗

Two types of micturitions of ileal neobladder.

Eight patients were evaluated clinically, radiologically, and urodynamically to determine the outcome of continent urinary diversion with ileal neobladder performed to treat the recurrent superficial bladder cancer after cystectomy with subcapsular prostatectomy. The mean age of the patients was 55.3 years. After descending dissection of the urinary bladder without ligation or dissection of Santorini's plexus, the prostate was cut to the bladder neck distally for 2 cm under the subcapular prostatectomy. One patient who had a short 3 cm intestinal segment between the pouch and the urethra, had severely prolonged micturition with peristalsis in this short segment, and required a re-operation. Micturition was good in the other seven patients, all with detubularized neobladder directly to the prostate capsule in anastomosis. Pressure flow studies performed on these seven patients revealed two types of micturition; "fast bladder" and "intermittent flow", the latter resembling detrusor sphincter dyssynergia.

Electromyography↗

[A case of posterior nutcracker syndrome occurring in pregnancy].

We have encountered a 23-year-old pregnant woman with macrohematuria, which occurred from the 8th or 9th week of gestation. Blood pressure and renal function were normal during the total course of pregnancy. Macrohematuria did not disappear after childbirth. Cystoscopy was conducted and the excretion of hematuria from the left ureter was confirmed. Therefore, a left renal venogram was performed although abdominal ultrasonography and CT scanning showed no abnormality. There were two branches of the left renal vein (LRV), such as the anterior and posterior branch. The pressure gradient was 4.4 cm H2O between the anterior branch of LRV and the inferior vena cava (i.v.c.). However, a significant pressure gradient (6.6 cm H2O) was demonstrated between the posterior branch of the LRV and IVC. From these findings we diagnosed this patient as venous hypertension in the posterior branch of the left renal vein (= posterior Nutcracker syndrome, PNS). Enlargement of the uterus in pregnancy might not be important in the occurrence of PNS because macrohematuria was observed from the 8th or 9th week of gestation. Functional hemodynamic change in pregnancy might cause a widening of the diameter or a shift of the aorta, that might result in compression of the posterior branch of the left renal vein. Persistence of macrohematuria after childbirth might have been due to irreversible hemodynamic alteration by the development of co-lateral circulation. To the best of our knowledge, this is the first case of PNS occurring in pregnancy.

Adult↗