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Biomedical subjects

T Tajima

Publications and source records attributed to T Tajima.

At least 181 records · Page 10Linked to original sources
PubMed1997

Pharmacokinetic study of aniracetam in elderly patients with cerebrovascular disease.

The clinical pharmacokinetics of the cognitive enhancer, aniracetam (200 mg), was studied in elderly patients with cerebrovascular disease (CVD) and compared with those of young healthy volunteers. Six female hospitalized patients (mean age 84.5 years) were used in this study. The serum level of anisic acid and p-methoxyhippuric acid, major metabolites of aniracetam, reached a peak at 2 h after oral administration, and returned to basal level by 6 h. Mean creatinine clearance was 20-30 ml/min. The t1/2 of metabolites was increased by 4- to 7-fold in the elderly patients compared with young volunteers. This study showed that tmax, t1/2, and AUC were enlarged in the elderly; however, no clinical side effects were observed.

Adult↗
PubMed1997

Clinical and biochemical aspects of thiamine treatment for metabolic acidosis during total parenteral nutrition.

We encountered six cases of total parenteral nutrition (TPN)-associated lactic acidosis during the 6-y period of 1988-1993. The patients were characterized by severe disease of the digestive organs, minimal food intake before surgery, and postoperative TPN with no food intake and with no vitamin supplements. Within 4 wk of TPN, they developed hypotension (< or = 80/60 mmHg), Kussmaul's respiration, and clouding of consciousness, as well as abdominal pain not directly related to the underlying disease. Routine laboratory examinations revealed no acute aggravation in hepatic, renal, or pancreatic functions. Arterial blood gas analysis showed pH < or = 7.134 and base excess < or = -17.5 mmol/L. Additional laboratory examinations revealed serum lactate > or = 10.9 mmol/L, serum pyruvate > or = 159 mumol/L, and lactate/pyruvate ratio > or = 0.029. None of the patients responded to sodium bicarbonate or other conventional emergency treatments for shock and lactic acidosis. After the first case, we suspected that thiamine deficiency might be responsible for this pathologic condition, Serum thiamine was proved to be < or = 196 nmol/L in 5 patients. Thiamine replenishment at intravenous doses of 100 mg every 12 h resolved lactic acidosis and improved the clinical condition in 3 patients. This article includes a review of 11 relevant reports published from 1982-1992 and a discussion of the biochemical mechanism of onset of thiamine deficiency-associated lactic acidosis. We emphasize the needs (1) to supplement TPN with thiamine-containing vitamins for the patients whose food intake does not meet nutritional requirements; (2) to monitor the patients routinely measuring serum thiamine concentration and erythrocyte transketolase activity during TPN; and (3) to intravenously replenish using high-dose thiamine simultaneously with the manifestation of signs and symptoms of lactic acidosis.

Acidosis, Lactic↗
PubMed1997

Analysis of the steroidogenic acute regulatory protein (StAR) gene in Japanese patients with congenital lipoid adrenal hyperplasia.

Genomic DNA from 19 Japanese patients with congenital lipoid adrenal hyperplasia (lipoid CAH) representing 16 different families was examined to identify the genetic alterations of steroidogenic acute regulatory protein (StAR). Ten of 19 patients had a 46,XX karyotype and nine had a 46,XY karyotype. Six of the 46,XX patients have experienced spontaneous pubertal changes including breast development and irregular menstruation whereas none of the 46,XY subjects displayed pubertal changes. Eight different mutations were identified. Sixteen patients were either homozygotes or compound heterozygotes for the Q258X mutation. The seven other mutations identified were 189delG, 246insG, 564del13bp, 838delA, Q212X, A218V and M225T. The 189delG, 246insG, 546del13bp and Q212X mutants encode truncated proteins. COS-1 cells transfected with expression vectors encoding cDNAs for the mutant StAR proteins which affect the C-terminus, 838delA, A218V and Q258X, exhibited no steroidogenesis enhancing activity. However, the M225T mutant retained some steroidogenic activity. The patient with the M225T mutation had late onset of this disorder and some capacity to secrete testosterone in response to hCG. These findings suggest: (i) that the Q258X mutation can be used as a genetic marker for the screening of Japanese for lipoid CAH, (ii) that the C-terminus of StAR plays an important role in the protein's activity and (iii) that there are differences in the extent of functional impairment of the testis and ovaries in lipoid CAH.

Adrenal Hyperplasia, Congenital↗
PubMed1997

A case of angiosarcoma of the breast.

This is a case report of a 20-year-old woman who had primary angiosarcoma of the left breast, with metastases to the spleen and ovary. Eight months after detecting a mass in her breast, she underwent mastectomy with biopsy of the ipsilateral axillary lymph nodes, splenectomy and bilateral oophorectomy. Five months after the operation, the patient succumbed to lung metastases. Angiosarcoma of the breast is a rare condition with a poor prognosis, and there are no established chemotherapeutic regimens as yet. Immunohistochemical staining for endoglin, known to be expressed mainly on the surface of endothelial cells, was positive. This suggests the possibility of treating angiosarcoma with anti-endoglin monoclonal antibodies.

Adult↗
PubMed1997

A case of multiple endocrine neoplasia type 2B.

A sporadic case of multiple endocrine neoplasia type 2B in a twenty-six year old man who manifested medullary thyroid carcinoma, multiple mucosal neuromas of the tongue and a marfanoid habitus is reported. At the time of diagnosis, he also had multiple liver and lung metastases. Genetic analysis of his lymphocytes revealed a point mutation in exon 16 of the RET proto-oncogene. Since multiple endocrine neoplasia type 2B has a relatively poor prognosis because of the occasional aggressive behavior of medullary thyroid carcinoma, the necessity of the genetic diagnosis of multiple endocrine neoplasia in the early stage is suggested.

Adult↗
PubMed1997

Lethality of the covalent linkage between mislocalized major outer membrane lipoprotein and the peptidoglycan of Escherichia coli.

The major outer membrane lipoprotein (Lpp) of Escherichia coli possesses serine at position 2, which is thought to function as the outer membrane sorting signal, and lysine at the C terminus, through which Lpp covalently associates with peptidoglycan. Arginine (R) is present before the C-terminal lysine in the wild-type Lpp (LppSK). By replacing serine (S) at position 2 with aspartate (D), the putative inner membrane sorting signal, and by deleting lysine (K) at the C terminus, Lpp mutants with a different residue at either position 2 (LppDK) or the C terminus (LppSR) or both (LppDR) were constructed. Expression of LppSR and LppDR little affected the growth of E. coli. In contrast, the number of viable cells immediately decreased when LppDK was expressed. Prolonged expression of LppDK inhibited separation of the inner and outer membranes by sucrose density gradient centrifugation, whereas short-term expression did not. Pulse-labeled LppDK and LppDR were localized in the inner membrane, indicating that the amino acid residue at position 2 functions as a sorting signal for the membrane localization of Lpp. LppDK accumulated in the inner membrane covalently associated with the peptidoglycan and thus prevented the separation of the two membranes. Globomycin, an inhibitor of lipoprotein-specific signal peptidase II, was lethal for E. coli only when Lpp possessed the C-terminal lysine. Taken together, these results indicate that the inner membrane accumulation of Lpp per se is not lethal for E. coli. Instead, a covalent linkage between the inner membrane Lpp having the C-terminal lysine and the peptidoglycan is lethal for E. coli, presumably due to the disruption of the cell surface integrity.

Amino Acid Sequence↗
PubMed1997

No genetic mutation in type II 3 beta-hydroxysteroid dehydrogenase gene in patients with biochemical evidence of enzyme deficiency.

Nonclassic or the mild form of 3 beta-hydroxysteroid dehydrogenase (NC3 beta-HSD) deficiency is an entity which is identified with typical features of premature pubarche, hirsutism, or oligomenorrhea. In this study, type II 3 beta-HSD gene from 4 girls who were diagnosed as NC3 beta-HSD deficient, base on the adrenal steroidogenic responses to ACTH, was analyzed to determine whether NC3 beta-HSD deficiency was an allelic variant of classical 3 beta-HSD deficiency by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). We could not detect any alterations of type II 3 beta-HSD gene from these patients. Our result strongly suggests that unlike classical 3 beta-HSD deficiency, NC3 beta-HSD deficiency may be secondary adrenal biosynthetic defects, rather than dual inherited deficiencies.

Adolescent↗
PubMed1997

Pubertal changes in testicular 3 beta-hydroxysteroid dehydrogenase activity in a male with classical 3 beta-hydroxysteroid dehydrogenase deficiency showing spontaneous secondary sexual maturation.

Males with classical 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency manifest appropriate secondary sexual maturation with an elevation in serum testosterone levels at pubertal age. To define the origin of serum testosterone, we evaluated a male patient with classical 3 beta-HSD who showed pubertal development. High values of testosterone and a ratio of delta(5) to delta(4) steroids in the spermatic vein indicated direct production of considerable amounts of testosterone and a persistent defect of 3 beta-HSD activity in the gonad. Immunohistochemical analysis showed distinct immunoreactivity in the Leydig cells of the patient. The patient was homozygous for a nonsense mutation in the type-II 3 beta-HSD gene. We propose that gonadal type-I 3 beta-HSD could be expressed by gonadotropin stimulation at pubertal age, and delta(4)-steroid precursors would convert to testosterone.

3-Hydroxysteroid Dehydrogenases↗
PubMed1997

Patency of the human accessory pancreatic duct as determined by dye-injection endoscopic retrograde pancreatography.

The accessory pancreatic duct (APD) is the smaller and less constant pancreatic duct. The patency of the APD was investigated clinically in an effort to determine its role in pancreatic pathophysiology. Dye-injection endoscopic retrograde pancreatography (ERP) was performed in 190 cases. In the patients who exhibited filling of the fine branches of the ducts on ERP, contrast medium with indigo carmine was injected into the major duodenal papilla. The patency of the APD was determined by observing the excretion of the dye from the minor duodenal papilla. Of the 123 control cases studied, 41% had a patent APD. According to the shape of the terminal portion of the APD on accessory pancreatogram, it was classified as either the stick type (n = 63), branch type (n = 15), saccular type (n = 15), spindle type (n = 11), or cudgel type (n = 8). In these groups, 49, 0, 27, 82, and 87% of the APD were patent, respectively. The patency of the APD in the patients with acute pancreatitis was 6% (1 of 17). The difference in patency between this group and the control group was significant (p < 0.01). The patency of the APD varies with the shape of the terminal portion of the APD. A patent APD may prevent acute pancreatitis by lowering the pressure in the main pancreatic ducts.

Acute Disease↗
PubMed1997

Association between serum gastrin levels, gastric acid secretion and age in early gastric cancer.

This study evaluated the effect of gastric acid secretion and serum gastrin response on tumor differentiation for early gastric cancer according to patients' age. We investigated the association between serum gastrin levels, gastric acid secretion and the histologic types of 335 early gastric carcinomas limited to the mucosal and submucosal layers in comparison with 450 gastric and 197 duodenal ulcers. The preoperatively examined basal acid output, maximal acid output and peak acid output after administration of tetragastrin and serum gastrin levels before and after ingestion of a test meal were determined. Patients with differentiated cancer and duodenal ulcer showed a significant negative correlation between gastric acid secretion and age, while the former group also had a significant positive correlation between serum gastrin levels and age. On the other hand, patients with undifferentiated cancer did not show any such correlation between gastric acid and age, but showed a significant positive correlation between serum gastrin, integrated gastrin response and age. Patients with gastric ulcer did not show any such correlations. These data suggest that both low acid secretion and endogenous hypergastrinemia, especially in the elderly, may play an important role in differentiated and undifferentiated gastric carcinomas.

Adenocarcinoma↗
PubMed1997

Three novel mutations and a de novo deletion mutation of the DAX-1 gene in patients with X-linked adrenal hypoplasia congenita.

The DAX-1 [DSS (dosage sensitive sex)-AHC critical region on the X, gene 1] gene is responsible for X-linked adrenal hypoplasia congenita (AHC). However, DAX-1 protein structure-function relationships are not well understood. Identification of missense mutations may help to reveal these relationships. We analyzed the DAX-1 gene from seven patients in six kindreds with X-linked AHC and identified one frameshift mutation, two missense mutations, and three deletion mutations. Case 1 had a 388delAG frameshift mutation, inducing a premature stop codon at position 70. Case 2 had a missense mutation, Lys382Asn, which encodes an asparagine (Asn) for lysine (Lys) at position 382. Sibling cases of 3-1 and 3-2 had a missense mutation of Trp291 Cys, which encodes a substitution of cysteine (Cys) for tryptophan (Try) at position 291. The tryptophan (Trp) at position 291 and lysine (Lys) at position 382 in human DAX-1 protein are highly conserved among other related orphan nuclear receptor superfamily members. Cases 4, 5, and 6 showed deletion mutation. In case 6, a de novo deletion mutation was revealed by both southern hybridization and polymerase chain reaction (PCR) of a GGAA tetranucleotide tandem repeat. These findings suggest that: 1) Trp at position 291 and Lys at position 382, located in the C-terminal presumptive ligand binding domain, are important to the functional role of the DAX-1 protein in adrenal embryogenesis and/or in hypothalamic-pituitary activity; and 2) molecular analysis of the DAX-1 gene may help genetic counseling, even in cases with deletion mutation, because a detection of de novo deletion may exclude another affected or carrier child.

Adrenal Insufficiency↗
PubMed1997

Molecular basis of nonclassical steroid 21-hydroxylase deficiency detected by neonatal mass screening in Japan.

Since 1989, neonatal mass screening for congenital adrenal hyperplasia (CAH) has been performed in Japan, and the frequency of the classical form of 21-hydroxylase deficiency was found to be nearly identical to that in other countries. However, it has not yet been determined whether our mass screening program can detect the nonclassical (NC) form. From 1991 to 1994, about 4,500,000 infants underwent CAH mass screening in Japan. During this period, we identified by screening 2 siblings and 2 unrelated patients who had mild elevation of serum 17-hydroxyprogesterone levels at 5 days of age, but who revealed no symptoms of CAH. They were diagnosed as having probable NC steroid 21-hydroxylase deficiency. To clarify the molecular basis of NC CAH detectable by neonatal screening in Japan, the steroid 21-hydroxylase (CYP21) genes from these cases were analyzed. The 2 siblings (patients 1 and 2) had I172N and R356W mutations in 1 allele and in the other allele had local gene conversion, including the P30L mutation in exon 1. Patient 3, who was unrelated, had gene conversion encoding the same P30L mutation in 1 allele and in the other allele had an intron 2 mutation (668-12 A-->G), causing aberrant ribonucleic acid splicing, and the R356W mutation. Patient 4, also a compound heterozygote, had the R356W and 707del8 mutations. The estimated rate of detection of the NC form by mass screening (1:1,100,000) seemed low compare to the established detection rate for the classical form (1:18,000). As all of our 4 patients were compound heterozygotes with at least 1 allele bearing 1 or more mutations associated with classic CAH, it may be difficult to detect NC cases carrying only NC-associated alleles using our current neonatal mass screening methods.

17-alpha-Hydroxyprogesterone↗
PubMed1997

Effects of vitamin K2 (menatetrenone) on atherosclerosis and blood coagulation in hypercholesterolemic rabbits.

Gamma-Carboxyglutamic acid (Gla)-containing protein, synthesized in the presence of vitamin K, has been found in atherogenic plaques, but the pharmacological effect of vitamin K on atherosclerosis is unclear. We examined whether vitamin K2 (menatetrenone) could affect the progression of both atherosclerosis and hypercoagulability in hypercholesterolemic rabbits. Vitamin K2 in daily doses of 1, 10 and 100 mg/kg was given with a 0.5% cholesterol diet for 10 weeks to 8 rabbits each. The plasma levels of total-cholesterol in the vitamin K2-treated groups were clearly lower than that of the hypercholesterolemic control group. The excessive dose of vitamin K2, even at the high dose of 100 mg/kg/day for 10 weeks, did not accelerate the progression of atherosclerosis and did not promote the coagulative tendency in the rabbits. In contrast, the vitamin K2 treatment (1 to 10 mg/kg/day) suppressed the progression of atherosclerotic plaques, intima-thickening and pulmonary atherosclerosis, the increase of ester-cholesterol deposition in the aorta, and both the elevation in plasma factor X level and increase in Hepaplastin test value in the rabbits. These results indicate that the pharmacological dose of vitamin K2 prevents both the progression of atherosclerosis and the coagulative tendency by reducing the total-cholesterol, lipid peroxidation and factor X activity in plasma, and the ester-cholesterol deposition in the aorta in hypercholesterolemic rabbits.

Animals↗
PubMed1997

Conventional molecular diagnosis of steroid 21-hydroxylase deficiency using mismatched primers and polymerase chain reaction.

We tested a conventional method based on polymerase chain reaction (PCR) and specific primers with one mismatched base at the 3' end to introduce restriction enzyme sites in order to detect mutations of the CYP21 gene without radioisotope. Using this method, the intron 2 mutation causing aberrant splicing of mRNA (In2G) and the exon 4 mutation (Ile->Asn, Ex4) in the CYP21 gene were analyzed. The nonsense mutation in exon 8 (Ex8NON) of the CYP21 gene was also investigated by PCR and subsequent restriction enzyme digestion. The mismatched primers successfully amplified the CYP21 gene containing the In2G and the Ex4 mutation sites, and the presence of these two mutations could be determined by restriction enzyme digestion after PCR. We used this new method to study 33 patients. Twenty-five of these patients were found to have at least one mutation (In2G and/or Ex4 mutation). By enzyme digestion after PCR, the Ex8NON mutation was also identified (7 out of 33 patients). In conclusion, we have developed a new method to detect point mutations in the CYP21 gene. This method was proved to be sensitive and rapid for the detection of the mutations studied. Therefore, this method is suitable for clinical genetic diagnosis.

Adrenal Hyperplasia, Congenital↗
PubMed1997

[Expectation of others' reward allocation, and ingroup favoritism in reward allocation].

The purpose of this study was to investigate people's expectation of others' ingroup favoritism, and the effect of expecting others to take part in reward allocation decision on ingroup favoritism in reward allocation. Subjects were randomly assigned to two groups, and were asked to rate attractiveness of ingroup members, and to allocate reward to ingroup and outgroup under two conditions. In the unilateral condition, the subject alone was to make the decision, and in the multilateral condition, every subject was to. The results indicated that equally in all conditions, subjects rated ingroup members more attractive, and expected others to allocate more reward to own groups. Reward allocation that favored ingroup occurred only under the multilateral condition, where everyone participated in reward allocation, regardless of whether the subject's own reward was dependent on others' decisions or was a fixed amount. The findings suggest that ingroup favoritism was not a result of quasi-strategy of self-interest in an attempt to maximize own gains, but of psychological group formation.

Adult↗
PubMed1997

[Pharmacokinetic, bacteriological and clinical studies on azithromycin in children].

Azithromycin (AZM) in fine granules was studied for its pharmacokinetics and clinical efficacies in eight child patients with ages between 1 month and 8 years. Informed consent was received from all of their parents. AZM was administered to the patients once a day at a dose of 10 mg/kg for 3 days. The clinical efficacies of AZM in 8 patients with microbial infections (pneumonia in one, Mycoplasma pneumonia in two, acute tonsillitis in one, pertussis in one, Campylobacter enteritis in one, infectious enteritis in one, Salmonella enteritis in one) were evaluated as "excellent" in five cases, "good" in two and "not evaluable" in one. As for the microbial efficacy, isolated strains were eradicated in 2 out of 3 patients. No adverse reaction was found except for one case with abnormal laboratory change, that is mildly increased GPT value. Plasma samples were collected from 3 cases. The elimination half-life of AZM was 45.8 hours. AUC0-infinity was 12.6 micrograms.hr/ml. Urine sample was collected from one. AZM concentration in urine was 35.0 micrograms/ml during a period between 48 and 72 hours after the start of treatment.

Anti-Bacterial Agents↗
PubMed1997

[Early HCC and adenomatous hyperplasia: evaluation of arterial and portal blood flow with CTA, CTAP, and pathologic correlation].

In order to analyze the hemodynamic properties of early hepatocellular carcinoma (HCC) and adenomatous hyperplasia (AH), three lesions (two HCCs, one AH) depicted as hypoattenuating at CTA and iso attenuating at CTAP were correlated with the histopathological findings. The number of normal hepatic arteries in the tumor was lower than in the liver. Degeneration and narrowing of the lumens were also seen microscopically. All tumors showed the replacing growth pattern and had similar numbers of the portal tracts in the tumor to the liver. The decreased number of intratumoral normal arteries is suspected to be a characteristic finding of the early stage of HCC.

Adenoma↗