Influence of non-inherited maternal HLA on disease development.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to K Matsuki.
Explore the source record for details and available documents.
We used a mixed leucocyte culture between human T cells and irradiated murine splenocytes which allowed us to distinguish between cytokine production from the responder and stimulator cells by the use of species-specific assays for mRNA up-regulation. Using this model of T cell activation by antigen, we studied the effects of human antigen-presenting cell-derived cytokines IL-1 beta, IL-6 and TNF-alpha on the activation of human T cell subsets. We show in this system that exogenously added IL-1 beta, IL-6 and TNF-alpha induces IL-2 receptor (R) up-regulation and IL-2 production, and proliferation by both CD4+ and CD8+ cells. The addition of IL-1 beta induces IL-6 mRNA, and anti-IL-1 antibodies or an IL-1R antagonist protein completely suppresses IL-6 and TNF-alpha supported proliferation. Similarly, addition of IL-6 or TNF-alpha induces up-regulation of IL-1 beta mRNA. However, anti-IL-6 and anti-IL-6R antibodies only partially block proliferation supported by IL-1 beta. These findings suggest that IL-6 and TNF-alpha will induce IL-2R up-regulation/IL-2 secretion via the induction of IL-1 beta production.
HLA-DRB1*04 gene variants were determined in apparently healthy Japanese with PCR-SSCP and PCR-RFLP, and HLA-B-DRB1*04 haplotype frequencies were estimated statistically. DRB1*0405, which consisted of 60% of the Japanese DRB1*04 gene pool, was associated strongly with HLA-B54. This association was observed only for DRB1*0405, and not for any other DR4 variants. DRB1*0403 and DRB1*0406, which share the same peptide sequence except for amino acid 37, were both associated with B35 and B62. DRB1*0407 was associated exclusively with B35. DRB1*0410 was associated with B60 and B61. B60 and B61, on the other hand, were associated only with DRB1*0410 and DRB1*0405. B35 was associated with all DR4 microvariants. With this possible exception, our calculation suggests that unique B-DR associations were present even for DR4 microvariants. The knowledge of HLA-B and DRB1*04 associations would be useful in clinical settings.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In previous studies, it has been suggested that the suppression of testicular androgen had inhibits bladder carcinogenesis. In this study we investigated which phase of bladder carcinogenesis is inhibited by the hormonal change of the hypothalamus-pituitary-testicular axis induced by the depot form of the LH-RH agonist. All rats were treated with 0.05% BBN in tap water for 8 weeks and were observed for the following 16 weeks. They were divided into five groups. Group 1 (Control group); The LH-RH agonist was not administered. Group 2 (Initiation group); The LH-RH agonist (depot form) was administered subcutaneously two weeks before and after the initiation of the experiment. Group 3 (Promotion group); The LH-RH agonist (depot form) was subcutaneously administered at intervals of 4 weeks starting 6 weeks after the initiation of the experiment. Group 4 (Full term group); The LH-RH agonist (depot form) was administered subcutaneously at intervals of 4 weeks starting from 2 weeks before the initiation of the experiment. Group 5 (Castration group); Bilateral orchiectomy was performed one week before the beginning of the experiment. From our results, the followings were suggested, (1) more intensive inhibition of bladder carcinogenesis was observed in the group which received the LH-RH agonist (depot form), compared with the Castration group, (2) the bladder carcinogenesis was more intensively inhibited when the LH-RH analogue (depot from) was given in the promotion phase and (3) not only testosterone but also the regulatory system of the hypothalamus-pituitary-testicular axis is related to the bladder carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
A 67-year-old male was admitted for detailed investigation of an abnormal chest roentgenogram showing a tumor shadow about 3 cm in diameter in the left S1+2. The shadow was surrounded by minute granular and striate shadows. Small cell carcinoma of the lung was diagnosed and chemotherapy was commenced, but without effect. Hypercalcemia and superior vena caval syndrome followed. Autopsy indicated highly specific calcinosis present in the left upper lobe peripheral to the primary disease. This calcinosis was observed subepithelially in bronchi and bronchioles, in the tunica intima of the veins, and in the alveolar septa. It could not be detected in the tumor or arterial or lymphatic systems. The calcinosis had been present prior to the development of hypercalcemia, and the density of the calcinosis was greatest close to the tumor, gradually decreasing with increased distance from the tumor. The calcinosis appeared to have been caused by some substance, and to have been accelerated by venous congestion, resulting in its unique distribution.
The functional residual capacity (FRC) has been measured by gas dilution technique (GA) and body plethysmographic technique (BP) using the panting maneuver (PA). However, this maneuver is difficult to perform for patients who experience discomfort in breathing, and in cases of chronic obstructive pulmonary diseases, the FRC value measured by panting maneuver overestimates the true FRC value. Thus, in order to minimize these factors, we measured FRC during non-panting breathing (NP) using a BP device (BX-82, Minato Co., Osaka) and compared the results with the usual two methods. One hundred healthy subjects (Group I), 72 patients with restrictive ventilatory disorder (Group II, %VC = 62.7%) and 66 patients with pulmonary emphysema (Group III, FEV1.0% = 44.9%) were studied. All measurements were performed under 0.5 Hz respiratory frequency. The non-panting FRC measurement was performed by closing the mouth shutter of the BP for about 500 msec at the end of both the expiratory and inspiratory phase. From the box volume change and mouth pressure change, lisajous curves were formed and fitted by linear regression method. From this regression line, the volume of FRC was calculated. The obtained data had no significant differences among them, and there was a significant relationship between each technique. The correlation coefficient of non-panting breathing technique in Group III was slightly poor compared with the other techniques, and we therefore tried to re-classify Group III into small groups according to the severity of obstruction. It was subsequently found that this technique did not have the tendency to give a higher FRC value with increase in obstructive disorder.(ABSTRACT TRUNCATED AT 250 WORDS)
Between 1986 and 1990, 69 patients underwent surgery either for thoracic aneurysm (27 patients) or aortic dissection (42 patients). Sixty one patients (88%) survived and 8 patients (12%) died after surgery. Main determinants of deaths in 4 patients with true arch aneurysm were bleeding from the sites of aortic clamping or anastomosis and intraoperative severe LOS. Three patients with acute type A dissection died from bleeding due to clamp injury or myocardial ischemia. The cause of death in the patient with chronic type B dissection was associated with brain damage due to hypoxia developed during left heart bypass. Postoperative cardiac, pulmonary, hepatic and renal functions were analyzed in the operative survivors. Cardiac functions were maintained well in all patients except two patients with chronic type A dissection. Four patients, one with true arch aneurysm, 2 with chronic type A and one with chronic type B dissection, required tracheostomy. The mean of maximum total serum bilirubin exceeded 4 mg/dl in the patients with true arch aneurysm, acute and chronic type A dissection. The level of serum creatinine showed slight increase in all patients but prophylactic peritoneal dialysis was performed in one patient with chronic type A dissection. In conclusion, the cause of deaths in most patients with thoracic aneurysm was due to inappropriate operative techniques and circulatory supports during surgery. Without the complication described above, the patients could tolerate surgery well.
Between 1986 and 1990, 24 patients with Stanford type A dissection (acute; 14, chronic; 10) underwent surgery through median sternotomy. The patients were divided into two groups by a duration of postoperative ICU stay for respiratory care. Six patients in the long-period group stayed in ICU for more than 15 days and 18 patients in the short-period group stayed for less than 15 days after surgery. Acuity of disease, age, sex, operation time, pump time, aortic clamp time, lowest esophageal temperature, amount of blood transfusion, arch manipulation for cerebral perfusion with or without arch reconstruction, occurrence of phrenic nerve palsy and other postoperative complications, postoperative cardiac, hepatic and renal functions were compared between two groups. Conclusions are as follows: 1) Arch manipulation for cerebral perfusion with or without arch reconstruction, phrenic nerve palsy, other complications (pericardial and pleural fluid accumulation, recurrent nerve palsy, postoperative bleeding and coronary spasm) and high serum creatinine level were main factors for prolonged postoperative ICU stay for respiratory care and 2) arch manipulation in the patients with chronic type A aortic dissection induced high incidence of phrenic nerve palsy.
The authors investigated the influences of recombinant human growth hormone (rh-GH) on rat urinary bladder carcinogenesis induced with N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Rats belonging to the control group (Group I, n = 19) were given 0.05% BBN in drinking water for 9 weeks, and the bladder was excised on the 22nd week after the initiation of BBN administration and inspected. All animals developed visible tumors in the bladder. The mean number of tumors per bladder was 11.26 +/- 5.21, and the mean total volume of tumors per bladder was 126.1 +/- 212.7 microliters. In all but one of the experimental groups (Group V) and in the control group, all animals developed visible tumors in the bladder. When 0.5 units of rh-GH was injected subcutaneously once a week from the week 1 through the week 6 (Group II; n = 20), the mean number of tumors and mean total volume of the tumors were 12.15 +/- 6.59 and 206.6 +/- 318.0 microliters, respectively. When the administration period of rh-GH was changed to between week 7 through the week 12 (Group III; n = 19), the mean number of tumors and mean total volume of the tumors were 16.95 +/- 7.07 and 204.5 +/- 317.7 microliters, respectively. When rh-GH was administered from the week 13 through the week 18 (Group IV; n = 19), the respective values were 16.79 +/- 10.75 and 213.4 +/- 274.6 microliters. In Group V (n = 19), which received only rh-GH from week 1 through the week 6, no tumors were detected. There were statistically significant differences in the mean tumor numbers between Groups I and III, Groups I and IV, and Groups II and III. The mean volume of individual tumor was the greatest in Group II, although the differences were not statistically significant in comparison with the other groups. Histologically, all tumors were transitional cell carcinoma in every group. There were no statistically significant differences in distributions of tumor stage and tumor grade between any groups. These findings suggest that rh-GH enhances the promotion of carcinogenesis of chemically induced rat urinary bladder cancer. It will be necessary to elucidate whether this effect of rh-GH is expressed by the somatostatin hypothesis of GH action, its direct action, or some other mechanisms.
Genetic polymorphisms of HLA antigens and HLA-linked serum complement components (C2, C4A, C4B and BF) were investigated in 79 Japanese patients suffering from psoriasis. HLA typing revealed increased frequencies of HLA-A1, A2, B39, Bw46, Cw6, Cw7 and Cw11. Among complement components, positive associations were obtained with C4A4 and C4B2 and a negative association with BFF. The major histocompatibility complex haplotype (supratype), HLA-A2-Cw11-Bw46-C2C-BFS-C4A4-C4B2-DRw8 is purported to be a new high-risk haplotype in Japanese patients with psoriasis. Analysis of patients with this supratype via pulsed field gel electrophoresis showed the existence of specific, extensive DNA deletions near HLA-DR genes, but no disease-specific patterns could be observed by means of this technique. The newly-found high-risk haplotype indicates racial and ethnic differences among psoriatic patients.
A suspension of zinostatin stimalamer (YM881), an antitumor protein antibiotic in iodized poppy oil-fatty acid ester, was injected into the hepatic artery of 2 patients who received surgical treatment of hepatic tumors. Single doses of 4 mg of zinostatin stimalamer were injected into the hepatic artery by Seldinger's method. Two and 4 weeks after the dose, tissue samples were collected from the tumor and non-tumor regions close to and distant (normal tissues) from the tumor, and zinostatin stimalamer concentrations in these tissues were assayed by RIA. In one of the two patients, plasma concentrations of the drug were also assayed. Concentrations of zinostatin stimalamer in the tumor tissues (381.8 ng/g) were about 55 times greater than those in the normal tissue (6.9 ng/g) in patient No. 1 (week 4), and about 17 times in patients No. 2 (13.9 ng/g in the normal tissue and 229.8 ng/g in the tumor tissues in week 2). Plasma concentrations were assayed in patient No. 2, and were 510.3 ng/ml after one hr., 385.3 ng/ml after 3 hrs., 184.4 ng/ml after 6 hrs., and 45.4 ng/ml after 24 hrs., with a half life of 7.1 hrs. These results indicate that zinostatin stimalamer suspended in iodized poppy oil fatty acid ester persisted in the hepatic tumor tissues at the high concentrations, when injected into the hepatic artery, but was eliminated fairly rapidly from the plasma.
In order to investigate the influence of respiratory frequency in the measurement of specific airway conductance (sGaw) during non-panting breathing, we examined specific airway conductance using a body plethysmograph (BX-82, Minato) in 20 stable pulmonary emphysema patients and 19 normal control subjects. Our body plethysmograph device can measure sGaw automatically without panting by making various corrections using a 16-bit microcomputer. We measured sGaw first at a flow of 0.5 L/sec during both inspiratory and expiratory ventilatory phases, then the respiratory frequency was changed from 0.5 to 1.0, 1.5 and 2.0 Hz. In normal control subjects sGaw, tidal volume and mouth flow significantly changed by increasing respiratory frequency, and there was a significant correlation between sGaw and mouth flow. In pulmonary emphysema patients, tidal volume decreased significantly by increasing respiratory frequency, and there was a significant correlation between sGaw and tidal volume, but sGaw and mouth flow did not change significantly by increasing respiratory frequency. These results suggest that specific airway conductance is influenced by respiratory frequency, possibly due to the change in tidal volume and mouth flow. It is necessary to standardize respiratory frequencies and mouth flows in the measurement of specific airway conductance during non-panting breathing.
Vogt-Koyanagi-Harada syndrome (VKH) is a systemic disorder involving many organ systems, including the eye, the ear, the skin, and the meninges. One of the important clinical features of the disease is its strong association with histocompatibility antigens HLA-DR4 and HLA-Dw15. To investigate this association at the DNA level, the polymerase chain reaction technique was used. The DR beta 1 DNA sequence was analyzed to determine which part played the most significant role in the disease process. Although the number of patients studied was small, these data showed that these probes were useful in investigating the HLA-DR subtypes related to VKH. All but one patient (19 of 20) had a specific sequence encoding amino acids 70 and 71 of the HLA-DR beta 1 molecule. The data suggest that the sequence that encodes for amino acids 70 and 71 and adjacent ones of the HLA-DR beta 1 molecule could contribute to disease susceptibility.
Analyses of HLA-DRB1 gene using polymerase chain reaction and sequence-specific oligonucleotide probes reveal that the amino acid sequence Glu-Gln-Arg-Arg-Ala-Ala-Val at positions 69-75 of the third hypervariable region (HVR) of HLA-DR beta 1 chain is significantly associated with HTLV-I-associated myelopathy (HAM). Since the frequency of this sequence in HTLV-I carriers is almost the same as that in controls from Kagoshima (an endemic area of HTLV-I), this sequence may be related to susceptibility to HAM rather than to susceptibility to HTLV-I infection. Since this third HVR functions as putative antigen-binding sites and T cell recognition sites, the amino acid sequence of positions 68-73 was analyzed in detail. The analysis reveals that Gln70 and Arg71 are relevant to the occurrence of HAM.
The nucleotide sequence of a HLA-DRB gene with a predominant subtype of DRw8 specificity in Japanese (DR8.1) was determined with single-stranded DNA enzymatically amplified by polymerase chain reaction (PCR). The sequence differs at a single amino acid from both of the published DRw8/Dw8.1 and DRw8/Dw8.2 sequences: isoleucine67(AUC) instead of phenylalanine67(TTC) in DRw8/Dw8.1 and serine57(AGC) instead of aspartic acid57(GAT) in DRw8/Dw8.2. On the other hand the DR8.1 and DRw8/Dw8.3 have the same amino acid sequence although one silent nucleotide substitution has occurred between the two sequences. These results indicate that Japanese DR8.1 specificity corresponds to DRw8/Dw8.3. Furthermore, an oligonucleotide probe specific for this sequence was synthesized and hybridized with 33 HLA-typed controls. This probe clearly distinguished the particular subtype from other DRw8 subtypes and specificities.
Restriction fragment length polymorphism (RFLP) of the two genes for complement C4A and C4B was studied in 56 Japanese patients with rheumatoid arthritis (RA) and 161 normal individuals. HindIII digestion revealed six common patterns, from which the segregation of three common RFLP-types were deduced; 32-15 kb, 32-25 kb, and 32-20-13-6.5 kb. The last type showed positive associations with C4B5 and HLA-DR4. In the RA patients, an increase of this type was found as well as a decrease of the 32-15 kb/32-25-15 kb heterozygotes.