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Biomedical subjects

O Matsumoto

Publications and source records attributed to O Matsumoto.

At least 19 recordsLinked to original sources

Klinefelter's syndrome in the male infertility clinic.

The clinical features of patients with Klinefelter's syndrome attending a male infertility clinic have been investigated in order to consider their assisted reproduction treatment options. Over 12 years, a total of 148 patients with sterility due to azoospermia had Klinefelter's syndrome. Eight patients were shown by fluorescence in-situ hybridization (FISH) on metaphase spreads to be mosaic (46,XY/47,XXY), and 140 patients showed only 47,XXY. Small testes were observed in 95% of patients and gynaecomastia was seen in 12.4%. Half of the patients showed hypergonadotrophic hypogonadism, while others showed normogonadism (usually hypergonadotrophic). Spermatozoa were observed in semen from one patient with mosaicism and one without. Three-colour FISH revealed hyperploidy in 2.7% and 2.3% of these spermatozoa respectively. Multiple-site testicular biopsies in five recent patients were performed and yielded a specimen with round and elongated spermatids in one patient with 47,XXY karyotype. This sample was cryopreserved for future intracytoplasmic sperm injection. At follow-up, 46% of couples had chosen artificial insemination with donor sperm, and none had chosen adoption. Two patients developed testicular tumours, one a mature teratoma and the other a Leydig cell tumour. Two patients required androgen replacement therapy.

Adult

Tamsulosin and chlormadinone for the treatment of benign prostatic hyperplasia. The Kobe University YM617 Study Group.

The recent introduction of selective alpha-adrenoceptor blockers adds a further therapeutic option for the treatment of benign prostatic hyperplasia (BPH). Tamsulosin, a selective alpha 1-blocker, has proved effective in relieving irritative and obstructive symptoms caused by BPH. To investigate whether the combination of tamsulosin with the anti-androgenic drug chlormadinone is of further therapeutic benefit, 80 patients randomly received tamsulosin 0.2 mg daily, chlormadinone 50 mg daily or a combination of tamsulosin 0.2 mg and chlormadinone 50 mg daily for 16 weeks. Greater improvement in subjective symptoms of BPH was obtained with either tamsulosin alone or in combination with chlormadinone than with chlormadinone alone. However, the greatest improvement in objective uroflowmetric data was obtained with chlormadinone in combination with tamsulosin. Thus, the combination of tamsulosin with chlormadinone appears to be more beneficial than either of these agents used as monotherapy. Further investigation is required to fully evaluate the therapeutic effects of this combination. After the trial period one-third of the chlormadinone and tamsulosin/chlormadinone-treated patients needed no further treatment due to the satisfactory relief of symptoms. At 12 months follow-up, however, one-fourth of the patients had undergone transurethral resection of the prostate (TUR-P) regardless of medication. This suggests a limitation of the medical treatment of BPH.

Adrenergic alpha-Antagonists

Crystal structure of a pyrimidine dimer-specific excision repair enzyme from bacteriophage T4: refinement at 1.45 A and X-ray analysis of the three active site mutants.

Crystallographic study of bacteriophage T4 endonuclease V, which is involved in the initial step of the pyrimidine dimer-specific excision repair pathway, has been carried out with respect to the wild-type and three different mutant enzymes. This enzyme catalyzes the cleavage of the N-glycosyl bond at the 5'-side of the pyrimidine dimer, and subsequently incises the phosphodiester bond at the apyrimidinic site through a beta-elimination reaction. The structure of the wild-type enzyme refined at 1.45 A resolution reveals the detailed molecular architecture. The enzyme is composed of a single compact domain classified as an all-alpha structure. The molecule is stabilized mainly by three hydrophobic cores, two of which include many aromatic side-chain interactions. The structure has a unique folding motif, where the amino-terminal segment penetrates between two major alpha-helices and prevents their direct contact, and it is incompatible with the close-packing category of helices for protein folding. The concave surface, covered with many positive charges, implies an interface for DNA binding. The glycosylase catalytic center, which comprises Glu23 and the surrounding basic residues Arg3, Arg22 and Arg26, lie in this basic surface. The crystal structures of the three active-site mutants, in which Glu23 was replaced by Gln(E23Q) and Asp (E23D), respectively, and Arg3 by Gln (R3Q), have been determined at atomic resolution. The backbone structures of the E23Q and R3Q mutants were almost identical with that of the wild-type, while the E23D mutation induces a small, but significant, change in the backbone structure, such as an increase of the central kink of the H1 helix at Pro25. In the catalytic center of the glycosylase, however, these three mutations do not generate notable movements of protein atoms, except for significant shifts of some bound water molecules. Thus, the structural differences between the wild-type and each mutant are confined to the remarkably small region around their replaced chemical groups. Combined with the biochemical studies and the difference circular dichroism measurements, these results allow us to conclude that the negatively charged carboxyl group of Glu23 is essential for the cleavage of the N-glycosyl bond, and that the positively charged guanidino group of Arg3 is crucial to bind the substrate, a DNA duplex containing a pyrimidine dimer. The amino terminal alpha-amino group is located at a position approximately 4.4 A away from the carboxyl group of Glu23. These structural features are generally consistent with the reaction scheme proposed by Dodson and co-workers.

Amino Acid Sequence

Structural composition of hammerhead ribozymes.

Eleven kinds of hammerhead ribozymes were designed and synthesized to investigate the structural composition of the complexes and to find suitable crystallization conditions, the substrate chains having been modified to prevent hydrolysis. Electrophoresis patterns indicated that the two strands except for the substrate chain form a binary complex and that they form a ternary complex when mixed with the substrate chain. Both complexes were crystallized. The crystal of the binary complex belongs to a Laue symmetry of 32 (space group of P321, P3(1)21, or P3(2)21) with cell dimensions of a = b = 53.4 and c = 59.4 A. The volume per one nucleotide allows the asymmetric unit to contain one binary complex. Our results suggest that the catalytic part forms a rigid ribozyme structure which induces a scissile reaction when the substrate is bound, in a similar manner to an enzyme protein.

Base Sequence

The significance of gonadotropin-releasing hormone test for predicting fertility after varicocelectomy.

To predict the surgical outcome in 30 infertile men with varicocele, endocrinologic evaluation by the GnRH test was performed before and 6 months after the high ligation of the left internal spermatic vein. Semen analysis was performed and the levels of basal T and PRL were examined preoperatively and 6 months postoperatively. In the pregnancy group, the preoperative excessive response of LH to the GnRH test decreased significantly after surgery. Significant reduction in the LH response is considered to be a valuable parameter for predicting fertility.

Adult

Müllerian duct cyst with 46, XYq-.

We report a case of a müllerian duct cyst associated with a 46, XYq- chromosome anomaly. Müllerian duct cyst is a consequence of the abnormal regression of paramesonephric derivative. In the past many different manifestations have been associated with the 46, XYq-, anomaly. We discuss the possibility that a müllerian duct cyst may be one clinical manifestation of 46, XYq-.

Adult

Müllerian duct cyst with 46, XYq-.

We report a case of a müllerian duct cyst associated with a 46, XYq- chromosome anomaly. Müllerian duct cyst is a consequence of the abnormal regression of paramesonephric derivative. In the past many different manifestations have been associated with the 46, XYq-, anomaly. We discuss the possibility that a müllerian duct cyst may be one clinical manifestation of 46, XYq-.

Adult

Common expression of parathyroid hormone-related protein and no correlation of calcium level in renal cell carcinomas.

BACKGROUND: Parathyroid hormone-related protein (PTHrP) is the predominant cause of humoral hypercalcemia of malignancy (HHM). METHODS: Using a PTHrP-specific monoclonal antibody (MoAb), 4B3, the authors investigated the immunohistochemical localization of PTHrP in formalin-fixed and paraffin-embedded sections of normal human kidney tissues and tissues from 42 human renal cell carcinomas obtained at operation or autopsy. RESULTS: In normal renal tissues, the distal tubules and collecting ducts showed positive immunostaining. PTHrP was detected in 40 of 42 renal cell carcinoma tissues (95%). Histopathologically, the granular cell subtypes of renal cell carcinomas tended to be more strongly positive than the clear cell subtypes. There was no significant correlation between the level of immunostaining and each patient's serum calcium level. CONCLUSION: PTHrP was commonly observed in renal cell carcinomas, and no significant correlation was seen between the intensity of PTHrP staining and the serum calcium level.

Antibodies, Monoclonal

Crystal structures of ribonuclease F1 of Fusarium moniliforme in its free form and in complex with 2'GMP.

RNase F1, a guanine-specific ribonuclease from Fusarium moniliforme, was crystallized in two different forms, in the absence of an inhibitor and in the presence of 2'GMP. The crystal structure of the RNase F1 free form was solved by the molecular replacement method, using the co-ordinates of the RNase T1 complex with 2'GMP, and was refined to a final R-factor of 18.7%, using the data extended to 1.3 A resolution. For the crystal structure of the RNase F1 complex with 2'GMP, the solution of the molecular replacement method was obtained on the basis of the co-ordinates of the RNase F1 free form, and was refined to a final R-factor of 16.8%, using the data up to 2 A resolution. The two crystal structures of the RNase F1 free form and the complex with 2'GMP are very similar to each other as reflected by a small root-mean-square displacement (r.m.s.d.) value of 0.43 A for all C alpha atoms. The main differences between the two structures are associated with binding of 2'GMP in the substrate recognition site in the loop between Tyr42 and Glu46. A structural comparison between RNase F1 and RNase T1 shows a substantial similarity between all the C alpha atoms, as evidenced by a r.m.s.d. value of 1.4 A. The loop from residues 32 to 38 was strikingly different between these two enzymes, in both its conformation and its hydrogen bonding schemes. The side-chain of a catalytically active residue, His92, is shifted away from the catalytic site in RNase F1 by 1.3 A and 0.85 A with respect to the corresponding positions in the RNase T1 free form and in the RNase T1 complex with 2'GMP, respectively. In the RNase F1 complex, the guanine base of 2'GMP has a syn conformation about the glycosyl bond, and the furanose ring assumes a 3'-exo pucker, which is different from that found in the complex with RNase T1. In the catalytic site of the RNase F1 complex with 2'GMP, one water molecule was observed, which bridges the phosphate oxygen atoms of 2'GMP and the side-chains of the catalytically important residues, His92 and Arg77, through hydrogen bonds. A water molecule occupying the same position was found in the RNase F1 free form. The significance of this water molecule in the hydrolytic reaction is discussed.

Amino Acid Sequence

Fracture through united vascularized bone grafts.

The secondary fracture rate in 53 patients undergoing vascularized bone transfer for long-bone reconstruction, with a follow-up period of at least 2 years, is evaluated in this report. Twelve fractures occurred in 10 patients. Characteristics of the fractures were: (1) most occurred at the tibia recipient site; (2) most occurred through the transferred vascularized bone segment, rather than at its junctions; and (3) all fractures occurred within 1 year following bone union. When the fracture occurred in adults, union was relatively easily obtained by application of simple external fixation; on the other hand, union was difficult to obtain in patients with congenital pseudarthrosis of the tibia.

Adult

[Ultrastructure of immotile spermatozoa obtained from infertile male patients].

We sometimes experienced infertile patients whose sperms had no motility but were not stained by Eosin Y. In this paper we report five cases of so-called "immotile spermatozoa". The ultrastructure of sperm tails was examined by transmission electrone microscope (TEM). These cases were selected from the out-patient population who attended infertility clinic of our department. The semen analyses showed that all the cases had sperm motility below 1% and more than 90% of the spermatozoa were proven alive. Family history revealed that one case had an infertile sibling. None of them had situs inversus, bronchiectasis and chronic sinusitis which are classic trias of Kartagener's syndrome. They had no symptoms of upper respiratory tract infection which was caused by the abnormality in the flagella of the respiratory tract. The TEM pictures of sperm tails showed partial deletion of inner dynein arms in two cases, lack of central microtubular doublets (so-called 9 + 0) in two cases and disarrangement of microtubular doublets in one case. For the treatment of these cases there is no effective means but AID. However, the rapid progress of IVF-ET techniques and a report that the spermatozoa from Kartagener's syndrome had showed penetration into eggs encouraged us to think the micromanipulation of spermatozoa with IVF-ET as a hopeful option of the treatment in the near future.

Adult

[Subpopulation of leucocytes in the semen from fertile and infertile men--immunohistochemical and flow-cytometric analysis].

It is hard to differentiate leucocytes from immature germ cells among many round cells in ejaculated semen. Recently monoclonal antibodies (MoAbs) which recognize surface antigen of various subtypes of leucocytes are available. In this study we applied a panel of MoAbs for leucocyte subpopulations (granulocytes, T-lymphocytes, B-lymphocytes, Monocytes/Macrophages and pan-leucocytes). Semen smears from 64 mild oligozoospermic patients and 5 fertile volunteers were stained by immunohistological technique (avidin-biotin-immunoperoxidase method). We found highly varying total leucocyte numbers ranging from 1200 to 2.2 x 10(8) per ejaculate. When comparing semen from infertile patients with those from fertile donors, statistically significant higher medians of total leucocytes, total granulocytes and monocytes/macrophages were seen in infertile group. We compared a total number of leucocytes obtained from conventional Papanicolaou staining with that from immunohistochemical staining. Both were almost identical but the former gave a little bit higher value, because of the difficulty in differentiating leucocytes from immature germ cell by Papanicolaou staining. Moreover we performed an experiment to evaluate the applicability of flow-cytometry (FCM) to count leucocytes in semen. Cells in the semen smears were stained with MoAbs recognizing the surface antigen shared by every leucocyte, and percentage of the leucocytes which were thus stained with MoAbs was compared with that determined by FCM. Results from FCM constantly gave lower value than these from immunostaining. This is probably because FCM could not differentiate leucocytes from contaminated non cell substances (e.g. cell debris). From the present study it is not adequate to use FCM for the detection of leucocytes in semen as applied in haematology. Further techniques to remove non-cellular substances should be established for its application in semen analysis.

Antibodies, Monoclonal

Preliminary crystallographic studies on hammerhead ribozymes.

Crystallization of hammerhead ribozymes was tried by the hanging drop vapor diffusion method. The crystals grown up to 0.5 x 0.05 x 0.05 mm3 in size gave diffraction patterns with about 5 A resolution using synchrotron radiation. The crystal was determined to be trigonal with space group P3(1) or P3(2) and cell parameters a = b = 49.6 A and c = 53.3 A.

Base Sequence

Idiopathic retroperitoneal fibrosis: a case of unilateral lesion.

Here we report a case of idiopathic retroperitoneal fibrosis, a unilateral case, which resulted in remission by ureterolysis with intraperitonealization. A 24-year-old female was hospitalized because of hydronephrosis. Many examinations were performed with the suspicion of malignant disease, but no apparent cause was detected. We suspected idiopathic retroperitoneal fibrosis and performed surgical exploration. The pathological diagnosis was retroperitoneal fibrosis. Ureterolysis with intraperitonealization of the ureter was performed. Six months later, marked improvement of the right hydronephrosis was observed without steroid therapy.

Adult

X-ray structure of T4 endonuclease V: an excision repair enzyme specific for a pyrimidine dimer.

The x-ray structure of T4 endonuclease V, an enzyme responsible for the first step of a pyrimidine-dimer-specific excision-repair pathway, was determined at a 1.6-angstrom resolution. The enzyme consists of a single compact domain classified into an all-alpha structure. This single domain has two distinct catalytic activities; it functions as a pyrimidine dimer glycosylase and as an apurinic-apyrimidinic endonuclease. The amino-terminal segment penetrates between two major helices and prevents their direct contact. The refined structure suggests the residues involved in the substrate binding and the catalysis of the glycosylation reaction.

Amino Acid Sequence