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Biomedical subjects

F Nakajima

Publications and source records attributed to F Nakajima.

At least 19 recordsLinked to original sources

Both HLA-B*1301 and B*1302 exist in Asian populations and are associated with different haplotypes.

A B13 split antigen was newly identified with three alloantisera in Japanese, and two B13 split antigens were found in a Thai family. To confirm the variation of B13 and understand the correspondence between the serologic splits and the published B13 alleles, B*1301 and B*1302, we determined the sequences of genes coding for these B13 splits. The common Japanese B13 allele was found to be B*1301, whereas another split antigen was shown to be coded by B*1302. Two B13 variants identified in a Thai individual corresponded to B*1301 and B*1302. Moreover, 57 B13-positive samples from several ethnic groups were examined using the PCR-SSO method. Differing from previous reports, both B*1301 and B*1302 were found in samples from Asian populations. These two alleles were separately associated with different antigens: HLA-B*1301 exhibited a strong association with A2, Cw10, DR12, and DQ7 antigens, whereas HLA-B*1302 was strongly associated with A30, Cw6, DR7, and DQ2 antigens. In addition, applying the PCR-SSCP method, B*1301 and B*1302 could also be simply distinguished from each other.

Alleles

A new HLA-C allele, Cw*1403, associated with HLA-B44 in Japanese.

An allele encoding an HLA-C antigen, tentatively called CX44, associated with HLA-B44 was identified as a new member of the Cw14 group, Cw*1403. The nucleotide sequence of Cw*1403 was closest to that of Cw*1401: five bases were different between the two alleles, in which three bases in Cw*1403 (two in exon 3 and one in exon 4) were the same as those of most HLA-C alleles. Two substitutions from guanine to adenine were found in the new allele, both of which are in exon 2, one at position 134 (61 of exon 2) and the other at position 201 (128 of exon 2). The former nucleotide substitution leads to the substitution of amino acid residue 21 from Arg to His, and the other substitution was synonymous. The former substitution was shared with Cw2, 3, 5, 13, and 15 alleles, and the latter was shared with Cw2, 4, 5, 8, 12, 13, 15 and 16 alleles. The other seven unrelated Japanese samples with CX44 were analyzed by a PCR-SSO method. It was confirmed that all the seven samples have the same substitutions as the sequenced allele, and the allele demonstrates a strong association with A33, B44, DR13, and DQ1, which are known to form a common haplotype in Japanese and Koreans.

Alleles

Non-selective effects of amiloride and its analogues on ion transport systems and their cytotoxicities in cardiac myocytes.

The effects of amiloride and its analogues (3',4'-dichlorobenzamil (DCB), 2',4'-dimethylbenzamil (DMB), 5-(N-ethyl-N-isopropyl)amiloride (EIPA) and 5-(N-methyl-N-isobutyl)amiloride (MIBA)) on cardiac ion transporters (Na+/Ca2+ exchanger, Na+/H+ exchanger, Na+ pump and Ca2+ pump) and their cytotoxicities were tested in cardiac myocytes. All the tested compounds showed concentration-dependent inhibitory effects on the ion transporters studied in canine cardiac sarcolemmal vesicles. The concentrations (microM) of amiloride, DCB, DMB, EIPA and MIBA required to produce 50% inhibition were > 1000, 19, 10, 83 and 84, respectively, for the Na+/Ca2+ exchanger; 130, 73, 63, 16 and 14 for the Na+/H+ exchanger; > 1000, 72, > 300, > 300 and > 300 for the Na+ pump; and > 1000, 37, 93, 90 and 70 for the Ca2+ pump, respectively. Furthermore, these agents induced cell death in isolated rat cardiac myocytes and the 50% lethal concentrations (microM) were > 1000, 9.2, 30, 16 and 17, respectively. These findings demonstrate that amiloride and its analogues have non-selective inhibitory effects on cardiac ion transporters and cytotoxicity in cardiomyocytes. When these drugs are employed as experimental tools to investigate the involvement of ion transporters in cell functions, the results must be interpreted with caution.

Amiloride

[Expression of GP160 mRNA in renal cell carcinoma: an attempt to predict the sensitivity of IFN-alpha therapy].

BACKGROUND: Alpha-interferon (IFN-alpha) has significant antitumor activity against advanced renal cell carcinoma (RC). Although numerous clinical trials reported major responses in approximately 15% of patients subjected to INF-alpha therapy, it has been impossible to predict which patients will respond to IFN-alpha. RC cell lines could be subdivided into those that are inhibited by IFN-alpha and those that are not. The expression of GP160 (Aminopeptidase a/kidney-associated differentiation antigens) correlated with resistance to IFN-alpha. In RC xenografts using a mouse model, though GP160(+) RC cell lines were resistant to IFN-alpha, GP160(-) RC cell lines were markedly sensitive to IFN-alpha. METHOD: In this study, we assayed 26 RC patients for the expression of GP160 in mRNA level using RT-PCR (reverse transcription polymerase chain reaction). RESULTS & CONCLUSION: In 23 (88.5%) patients GP160 mRNA expression are remarkable as in normal kidney tissue, but in 2 (7.7%) patients, GP160 mRNA expression was weak. And in 1 (3.8%) patient, GP160 mRNA expression was hardly detectable, and in this patient complete remission was achieved with IFN-alpha therapy for advanced lung and mediastinal metastatic RC.

Adult

[Primary seminoma of the prostate and embryonal cell carcinoma of the left testis in one patient: a case report].

A 27-year-old Japanese male presented with gross hematuria and right frank pain, and was diagnosed of having a right ureteral stone by IVP. Though the stone was passed spontaneously, gross hematuria continued, and his urinary stream became week. The prostate was moderately enlarged. The prostate biopsy was initially thought to represent prostate rabdomyosarcoma. He underwent a pelvic extenteration followed by chemotherapy with dacarbazing and ADM. Three years after the pelvic exenteration, coin lesions were found on a chest X-ray film. He was diagnosed as embryonal cell carcinoma of the left testis with pulmonary metastasis and received 3 courses of PVB therapy. At this time, the former diagnosis of prostatic rabdomyosarcoma was changed to prostatic rabdomyosarcoma was changed to prostatic seminoma, because placental-ALP staining was positive. This patient had two distinct germinal cell tumors in the prostate and the left testis. He was alive without any tumor recurrence 20 months after PVB chemotherapy. To the best of our knowledge our report represents the first patient of seminoma of the prostate in the world.

Adult

Identification of the gene encoding a novel HLA-B39 subtype. Two amino acid substitutions on the beta-sheet out of the peptide-binding floor form a novel serological epitope.

Serological analysis suggests the existence of a novel HLA-B39 subtype (HLA-B39N) in the Japanese population. To identify this novel allele, a gene encoding HLA-B39N was cloned and the exons were sequenced. A gene encoding HLA-B39N (B*3904) and B*39011 differs by two nucleotide substitutions at codons 11 and 12 whereas B*3904 and B*39013 differ by three nucleotide substitutions at codons 11, 12, and 312. One nucleotide difference at codon 11 produces a change from serine in B*3901 to alanine in B*3904 whereas another difference at codon 12 changes valine in B*3901 to methionine in B*3904. The residues 11 and 12 are located on the beta-sheet out of the peptide-binding floor and are completely buried in the molecule. These results suggest that the substitutions at these residues alter the conformation of other residues forming epitopes of alloantibodies. Analysis of HLA-B*3901 genes in the Japanese population showed that both B*39011 and B*39013 were observed in the Japanese population. The present study suggests that B*3904 may have evolved from B*39011 rather than B*39013.

Amino Acid Sequence

Effects of ouabain on muscle tension and intracellular Ca2+ level in guinea-pig aorta.

The effects of ouabain on muscle tension and the intracellular Ca2+ level ([Ca2+]i) were examined in guinea-pig aorta loaded with fura-2. Ouabain caused a gradual and sustained increase in both [Ca2+]i and muscle tension. There was a positive correlation between these two parameters. In Ca(2+)-free solution, ouabain did not affect either [Ca2+]i or muscle tension, suggesting that the ouabain-induced increase in [Ca2+]i was not due to Ca2+ release from storage sites. The ouabain-induced increase in [Ca2+]i and muscle tension was inhibited by Ni2+, which inhibits the Na+/Ca2+ exchanger, but not by verapamil. Furthermore, anionic and cationic amphiphiles were used as modulators of the Na+/Ca2+ exchanger. Sodium dodecyl sulfate accelerated the responses to ouabain, whereas dodecyltrimethylammonium bromide inhibited them. These results suggest that in the guinea-pig aorta, ouabain induces contraction by increasing the Ca2+ influx through the Na+/Ca2+ exchanger on the plasma membrane, but not through verapamil-sensitive Ca2+ channels.

Animals

[Recombinant human granulocyte-colony stimulating factor (rhG-CSF) treatment for spleen abscess and periostitis in a patient with chronic granulomatous disease].

A 9-year-old boy with chronic granulomatous disease was hospitalized on May, 1991, because of continued fever and pain in the right elbow. Increased bone intensity at the distal end of right humerus on x-ray and a 33 x 36 mm space-occupying lesion in the spleen on abdominal CT scan were recognized. Under a diagnosis of periosteitis and spleen abscess, intravenous infusion of rhG-CSF at a dose of 200 micrograms/m2/day was started in combination with antimicrobial therapy. Fever, tenderness, swelling in the right elbow and inflammatory indices improved three weeks after the institution of therapy. Hydrogen peroxide (H2O2) formation by neutrophil increased significantly, although intermittently, during the therapy. The spleen abscess had completely vanished on CT scan on February, 1992. The therapy was well tolerated and no significant side effects were observed. The use of rhG-CSF in combination with potent antibiotics is recommended for patients with serious infections in chronic granulomatous disease to avoid a fatal course.

Abscess

Treatment for stage III-IV neuroblastoma patients: initial response to chemotherapy evaluated by biochemical parameters.

Fourteen patients with stage III-IV neuroblastoma were treated with alternating combination chemotherapy consisting of (a) VP16/cisplatin and (b) doxorubicin/vincristine/cyclophosphamide. The initial response to induction chemotherapy, especially to VP16/cisplatin was evaluated by determining t 1/2 for urinary vanillylmandelic acid (VMA), homovanillic acid and serum neuron specific enolase (NSE). The period prior to normalization of these parameters was also determined. The patients could be classified as 7 rapid responders, with less than 3 weeks of t 1/2 VMA, or t 1/2 NSE, and 7 slow responders longer than 4 weeks of t 1/2 VMA. An analysis of the data indicates that an initial rapid response correlated with subsequent high complete response rate, but did not necessarily predict better prognosis in these patients.

Abdominal Neoplasms

[The suction effusion fluid is useful as a sample for blood biochemistry].

We examined whether the suction effusion fluid could be used as a new sample for blood biochemistry. The fluid was obtained from the skin surface of female mongrel dogs by transcutaneous suction after removal of the horny substance. The appropriate intraluminal pressure for suction was 300 mmHg at which the effusion fluid flow rate was 0.6 microliter/min/cm2. The blood biochemistry examination revealed that the creatinine (Cr) and urea (BUN) concentrations in the suction effusion fluid were similar to those in plasma and that the protein and lipid concentrations were much smaller than those in plasma. The six-hour study showed that the effusion fluid could be obtained for hours at the same skin area and that the Cr and BUN concentrations were consistently close to those in plasma. In uremia models, the Cr and BUN concentration in the suction effusion fluid was similar to and had an extremely high correlation (r = 0.985 and 0.982 respectively) to that in plasma through out the range for clinical practice. The skin biopsy revealed that the regeneration of the horny substance had started at one week after the suction and complete recovery was seen at four weeks. The invasiveness of the suction seemed to be small. The suction effusion fluid is a reliable material for measurement of Cr and BUN in plasma and, as it contains much less proteins and lipids, will be a good sample for biosensors.

Animals

[Posterior fossa hemorrhage 11 years after the use of silastic dural substitute: case report].

A case of posterior fossa hemorrhage is reported. The hemorrhage occurred 11 years after posterior fossa craniotomy with closure using a graft of silastic dural substitute. This 14 year-old girl underwent suboccipital craniotomy at the age of 3 years because of traumatic posterior fossa hemorrhage. The dura mater was repaired with a piece of dural substitute. Eleven years later, she developed severe headache and vomiting. Computerized tomography scanning revealed a high density area in the right posterior fossa. At exploration, a fresh clot was evacuated between the dural graft and the fibrous scar tissue. The resected fibrous scar tissue was 1cm thick, and was adhering to the duro glial scar tissue. Her postoperative course was uneventful, and she was discharged 2 weeks after surgery. Microscopic examination of the fibrous scar tissue revealed an outer layer of loose connective tissue with numerous capillaries. The inner layer consisted of dense connective tissue. It was speculated that fragile capillaries of fibrous scar tissue caused this hemorrhage. Surgeons should not forget this complication although silastic dural substitute is less used than it used to be.

Adolescent

[Simultaneous occurrence of renal cell and transitional cell carcinoma in the same kidney and ureter. A case report].

An unusual case of 2 concurrent primary renal tumors within the same kidney is reported. A 70-year-old woman presented with gross hematuria when she was in the hospital for cerebral infarction. Excretory urography revealed a marked expansion of the right kidney with no renal function. CT scan showed a mass arising from the right kidney, the hydronephrotic right renal pelvis, and a mass in the lower right ureter. Selective renal angiogram showed marked neovascularity of the mass. There was an encasement of the intrarenal artery to the lower pole. Angiographic findings were highly suggestive of a renal cell carcinoma with a second neoplasm in the renal pelvis. Subsequently, the patient underwent right radical nephroureterectomy and partial cystectomy. Section of the removed specimen revealed a 4.0 X 3.8 cm solid tumor confined to the kidney in the upper pole and a transitional cell carcinoma arising from the renal pelvis. In addition, transitional cell carcinoma was present in the distal ureter.

Aged

[Absorption of tetrahydropyranyl adriamycin administered intravesically immediately after transurethral resection of bladder carcinoma].

Absorption of tetrahydropyranyl adriamycin (THP) administered immediately after transurethral resection of bladder carcinoma (TUR-Bt) has not been reported. In this study, we have examined the absorption of THP and the systemic toxicity in the early post-TUR period. Of 21 patients with bladder carcinoma, 10 had a solitary tumor and 11 multiple tumors. Twenty mg THP in 40 ml of sterile water was intravesically administered on days 1, 3, 5, 7, 14 and 28, and then every 4th week. The THP solution was retained for 2 hours. The blood THP concentration was measured 30 minutes and 2 hours after the intravesical administration on days 1, 7 and 28. No systemic side effects were observed. Thirteen of the 38 (34%) samples contained a detectable level (more than 1 ng/ml) of THP on the post-TUR-Bt on day 1, 8, of 42 (19%) on day 7, and 3 of 18 (17%) on day 28. Altogether, 24 of the 98 (24%) samples contained more than 1 ng/ml THP. The highest blood THP level was 23 ng/ml on day 1. The differences between frequency of detection of blood THP in the samples at 30 minutes and 2 hours were not statistically significant. The difference between average concentration of blood THP of patients with solitary and multiple tumors also was not significant. These results indicate that intravesical THP administration starting within 24 hours after TUR-Bt can not result in significant systemic absorption of THP, and the systemic toxicity can be avoided.

Absorption

[Atresia hymenalis with acute urinary retention: a case report].

We report a case of atresia hymenalis in a 14-year-old girl presenting with a clinical symptom of acute urinary retention. On physical examination she was found to have a lower abdominal mass and an imperforate bulging hymen. She underwent hymenal incision, and subsequently the symptom disappeared. It is very uncommon for atresia hymenalis to manifest itself with acute urinary retention as the first clinical sign, but we should consider this disease if a pubertal girl seeks medical opinion for acute urinary retention.

Acute Disease

Structure of the so-called 'prismless' enamel in human deciduous teeth.

The surface enamel of human deciduous teeth showing a more negative birefringence by polarized light was investigated by differential interference contrast microscopy and by scanning electron microscopy (SEM) following EDTA etching. Though this surface enamel has been generally called the 'prismless' enamel, in this study, the so-called 'prismless' enamel was categorized into 'false', 'moderate', 'essential' and 'complex' types according to whether they took the form of distinct prisms which bended at the subsurface, indistinct circularly based prisms or not. Based on the SEM observations some types of the 'prismless' enamel showed parallel crystallites and no prism boundaries. However, if indistinct prisms showing centripetal crystallites within the circular boundaries are admitted into the prismless enamel, other types except the 'false' one will generally belong to it.

Birefringence

Distribution patterns of the surface "prismless" enamel in human deciduous incisors.

Distribution patterns of the "prismless" enamel were investigated in the labial, lingual, and proximal surfaces of human deciduous incisors under transmitted light through a differential interference contrast. The "prismless" enamel was generally either a short-length (0.2-0.3 mm) type, including island-like and isolated step-like shapes, or a long, band-like type, including relatively short (0.5-1 mm) and longer (2-5 mm) shapes. The island-like type was commonly observed at various intervals in the surfaces; the isolated step-like type was relatively rare. The longer band-like type was found in the maxillary labial and maxillary and mandibular proximal surfaces, but, in the other surfaces, this type was not seen. The surface enamel possessing the longer band-like type was also higher in the ratio of the total length of the "prismless" enamel to the whole surface length than the other surfaces. The frequency of the "prismless" enamel tended to be higher in the cervical region and lower towards the incisal edge.

Child