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Biomedical subjects

S Kagawa

Publications and source records attributed to S Kagawa.

At least 163 records · Page 9Linked to original sources

[A case of penile revascularization by Hauri's method for arteriogenic impotence].

In a 35 year old arteriogenic impotent patient without a history of hypertension, arteriosclerotic disease, or diabetes mellitus, the corpus cavernosum of the penis was revascularized using Hauri's method. Before surgery, erection after the intra-cavernous injection of 20 micrograms of prostaglandin E1 was very weak. In a color ultrasonography the peak systolic velocity of the cavernous arteries was recorded as being only 18 cm/sec. Furthermore, no artery except the right dorsal artery was evident even with a digital subtraction angiography. Accordingly he was diagnosed as having arteriogenic impotence, and we carried out the corpus cavernosum revascularization using Hauri's method under microscopic magnification. The dorsal artery and the deep dorsal vein were anastomosed side-to-side, and the hypogastric artery and dorsal artery were anastomosed end-to-side. After the revascularization surgery, the peak systolic velocity of cavernous arteries returned to normal (53 cm/sec), and the penis showed complete erection after an intracavernous injection of 20 micrograms of prostaglandin E1. Before surgery this patient had no experienced sexual intercourse, but he could achieve full sexual intercourse 2 weeks after the surgery. His erectile ability has been maintained for 4 months since the surgery. This is the 1st case of arteriogenic impotence treated using Hauri's method in Japan.

Adult↗

[Postoperative results of ligation of crura penis for impotence with corporal veno-occlusive insufficiency].

We performed ligation of the crura penis for 34 impotents with corporal veno-occlusive insufficiency without arterial insufficiency and neural dysfunction from October 1987 to April 1991. Ages ranged from 24 to 72 (52.6 +/- 12.7) years old and follow up period was from 1 to 41 (17.7 +/- 12.6) months. For six patients ligation of the crura only was performed, for 22 ligation of the crura and deep dorsal vein (DDV) as well was performed at the same time, and for 6 crural ligation was performed after ligation of DDV. These operations required less than one hour and there were no severe complications. The postoperative results at 1 month were as follows: Excellent (sufficient spontaneous erection was recovered); 18, Improved (complete erection with intracavernous papaverine injection was achieved); 13, and Failure; 3. Erectile function was maintained only in 50% of the 18 pts. graded excellent. Ninety percent of the 31 patients graded either excellent or improved could maintain erectile function after 40 months with papaverine injection. Venous surgeries could not be a primary treatment for correcting the outflow abnormalities (of the veins). So it is conceivable that failure or recurrence could occur during a long follow up period. We concluded that crural ligation was acceptable as the first line treatment for erectile dysfunction due to corporal veno-occlusive insufficiency because of its relative non-invasiveness compared to other venous surgeries.

Adult↗

[Gene expressions of type IV collagenase and tissue inhibitor of metalloproteinases (TIMP) in human bladder cancers].

Matrixmetalloproteinases (MMP), such as type IV collagenases and interstitial collagenases, play an important role in tumor invasion and metastasis. And tissue inhibitor of metalloproteinases (TIMP) inhibit collagenolytic activity of these enzymes. We investigated the gene expressions of MMP-9 (92 kDa type IV collagenase), MMP-2 (72 kDa type IV collagenase), TIMP-1 and TIMP-2 in bladder cancers by Northern blot and slot blot hybridization. The mRNA levels of MMP-2, TIMP-1 and TIMP-2 increased in the cases with invasion and metastasis of bladder cancers. These findings suggest that MMP-2 acts as a regulator of the invasion and metastasis of bladder cancers. The MMP-2/TIMP-2 ratio increased as tumor invasion and metastasis progressed, suggesting that an imbalance in the MMP and TIMP ratio promote the invasion and metastasis of bladder cancers. And we also investigated the gene expressions of c-fos that activate the collagenase genes, and there was a correlation between c-fos and MMP-2 in gene expressions. It is suggested that fos gene may play an important role for the invasion and metastasis in bladder cancers.

Aged↗

[Detection of methicillin-resistant Staphylococcus aureus using PCR and non-radioactive DNA probes (II)].

Methicillin resistance in staphylococci is primarily due to the presence of a mec A gene which encodes the novel penicillin-binding protein 2'. Some chromosomal factors, fem A and fem B, also participate in the expression of methicillin resistance in S. aureus. This study was designed to detect mec A, fem A and fem B genes for identification of staphylococcal species and for discrimination of methicillin-resistant cells. Three different pairs of DNA primers (PBP2'AF-PBP2'AR, fem AF-fem AR and fem BF-fem BR) complementary to unique regions of mec A, fem A and fem B genes were synthesized for use in polymerase chain reaction with DNAs of methicillin-sensitive S. aureus (MSSA), S. epidermidis, methicillin-resistant S. aureus (MRSA) and S. epidermidis. Amplified target DNAs of 630, 509, and 651 bp were resolved on ethidium bromide-stained gel, and hybridized to DNA probes conjugated to alkaline phosphatase. When applied to pure cultures on the MRSA screen agar, all three DNA probes tested detected MRSA in 47 of 61 culture-positive specimens (77.1%); the detection ratio of MRSA with mec A and either fem A or fem B probes was increased to 95.9%. By contrast, the fem A and fem B probes did not detect S. epidermidis. The result of detecting these species streaked on mannitol-salt agar were similar, while the detection of MSSA with the fem A and fem B probes was incomplete irrespective of the presence or absence of mec A. These findings suggest a good correlation between cultivation and DNA probe assay with respect to MRSA detection.

DNA Probes↗

[MRSA--detection of mecA and its regulatory genes].

Methicillin resistance in S.aureus and S.epidermidis strains is primarily due to production of a new penicillin-binding protein PBP2' with extremely low binding affinity to most beta-lactam antibiotics. The structural gene for PBP2', mecA, is detectable in clinical specimens by using the polymerase chain reaction (PCR). Amplified target DNA of 630bp can be resolved on ethidium bromide-stained gels, and hybridized with a probe conjugated to alkaline phosphatase. Survey for the mecA gene in 304 staphylococci revealed a good correlation between the presence of mecA and cultivation on agar plates with 4 micrograms/ml of oxacillin, although 3% of sensitive S. aureus strains had the mecA gene. On the other hand, analysis of the regulatory genes (orf 1 and 2) of methicillin resistance was performed on methicillin-resistant S.aureus strains N315 and MR108, demonstrating that the genome of MR108 lacks orf 2 which encodes the repressor protein (Hiramatsu et al., see Ref.5). The regulatory genes of mecA were surveyed for 192 staphylococci by using PCR and allele-specific oligonucleotide probes: 76% of resistant S. aureus strains and 48% of resistant S. epidermidis strains possessed orf 1 corresponding to MR108 (constitutive-type strain), while the remainder of the resistant strains and two strains of sensitive S. epidermidis had two orfs of N315 (inducible-type strain). Furthermore, it appeared that mutation of the femA gene might not be an additional factor for expression of methicillin resistance. These observations suggest that mecA and its regulatory genes should be examined to understand how the genetic background contributed to the phenotypic expression of methicillin resistance in clinical strains.

Base Sequence↗

Demonstration that a human 26S proteolytic complex consists of a proteasome and multiple associated protein components and hydrolyzes ATP and ubiquitin-ligated proteins by closely linked mechanisms.

It is known that two types of high-molecular-mass protease complexes are present in the cytosol of mammalian cells; a 20S latent multicatalytic proteinase named the proteasome, and a large proteolytic complex with an apparent sedimentation coefficient of 26S that catalyzes ATP-dependent breakdown of proteins conjugated with ubiquitin. In this work, we first demonstrated that a low concentration of SDS was required for activation of the latent proteasome, whereas the 26S complex degraded substrates for proteasomes in the absence of SDS. Moreover, the 26S complex was greatly stabilized in the presence of 2 mM ATP and 20% glycerol. Based on these characteristics, we next devised a novel procedure for purification of the 26S proteolytic complexes from human kidney. In this procedure, the proteolytic complexes were precipitated from cytoplasmic extracts by ultracentrifugation for 5 h at 105000 x g, and the large 26S complexes were clearly separated from the 20S proteasomes by molecular-sieve chromatography on a Biogel A-1.5 m column. The 26S enzyme was then purified to apparent homogeneity by successive chromatographies on hydroxyapatite and Q Sepharose, then by glycerol density-gradient centrifugation. Electrophoretic and immunochemical analyses showed that the purified human 26S complex consisted of multiple subunits of proteasomes with molecular masses of 21-31 kDa and 13-15 protein components ranging in molecular mass over 35-110 kDa, which were directly associated with the proteasome. The purified 26S proteolytic complex degraded 125I-labeled lysozyme-ubiquitin conjugates in an ATP-dependent manner. The 26S enzyme also showed high ATPase activity, which was copurified with the complex. Vanadate and hemin strongly inhibited not only ATP cleavage, but also ATP-dependent breakdown of ubiquitinligated proteins, suggesting that the 26S complex hydrolyzes ATP and ubiquitinated proteins by closely linked mechanisms. These findings indicate that the 26S complex consists of a proteasome with proteolytic function and multiple other components including an ATPase that regulates energy-dependent, ubiquitin-mediated protein degradation.

Adenosine Triphosphatases↗

cDNA cloning of rat proteasome subunit RC1, a homologue of RING10 located in the human MHC class II region.

The nucleotide sequence of a cDNA that encodes a new subunit, named RCl, of rat proteasomes (multicatalytic proteinase complexes) has been determined. The polypeptide predicted from the open reading frame consisted of 208 amino acid residues with a calculated molecular mass of 23, 130, which is consistent with the size obtained by electrophoretic analysis of purified RCl. The partial amino acid sequences of several fragments of RCl, obtained by protein chemical analyses, were found to be in excellent accordance with those deduced from the cDNA sequence. Surprisingly, the overall structure of RCl was found to be almost identical to that of recently isolated RING10, whose gene is located in the class II region of the human MHC gene cluster. This finding suggests that RCl is a homologue of human RING10, supporting the proposal that proteasomes are involved in the antigen processing pathway.

Amino Acid Sequence↗

Intra-arterial adriamycin chemotherapy in combination with radiotherapy for advanced bladder cancer.

A total of 38 patients with locally advanced bladder cancer (T2, n = 14; T3, n = 14; T4, n = 10) were treated with intra-arterial Adriamycin chemotherapy in combination with radiotherapy. The clinical as well as the pathological efficacy of this treatment was evaluated in all patients. Clinically, 23 (60.5%) of the 38 patients achieved a complete remission (CR), 12 (31.6%) achieved a partial remission (PR), and 3 (7.9%) remained stable (NC). The pathological efficacy was evaluated according to the criteria of Shimosato et al., with 20 (52.6%) of the 38 patients being categorized as grade IV; 2 (5.3%), as grade III; 12 (31.6%) as grade II; and 4 (10.5%), as grade 0. The 5-year actuarial survival as a function of clinical stage amounted to 91.6% for T2, 50.0% for T3, and 37.4% for T4 (T2 vs T3, P less than 0.05; T2 vs T4, P less than 0.01). The 5-year actuarial survival determined according to the clinical and the pathological efficacy of treatment were 74.1% for CRs, 56.2% for PRs, and 0 for NCs (CR vs NC, P less than 0.01; PR vs NC, P less than 0.01). Surgery for preservation of the bladder was performed in 30 of the 33 patients who achieved clinical and pathological CRs or PRs. The 5-year actuarial survival of these 30 patients was 73.2%. These results demonstrate that this therapy is a useful method for the treatment of locally advanced bladder cancer and that preservation of the bladder might be feasible in patients who achieve clinical and pathological CRs or PRs during this treatment.

Adenocarcinoma↗

The 4th study of prophylactic intravesical chemotherapy with adriamycin in the treatment of superficial bladder cancer: the experience of the Japanese Urological Cancer Research Group for Adriamycin.

A multicentric randomised trial was conducted for the purpose of investigating the efficacy of intravesical chemoprophylaxis of superficial bladder cancers. A total of 443 patients (number of evaluable patients, 284) were registered from July 1987 to December 1989 and randomised into 3 groups. Group A received 21 intravesical instillations of Adriamycin (ADM) at 20 mg/40 ml physiological saline for 2 years after undergoing transurethral resection (TUR); group B was given the same dose as group A but received 6 intravesical instillations for 2 weeks before undergoing TUR; and group C served as a control and underwent TUR only. Better prophylactic effects were obtained in group A. The overall non-recurrence rates calculated for groups A and B differed significantly (P less than 0.05) on day 240, and those determined for groups A and C were also significantly different (P less than 0.01) on day 480. No benefit was obtained using intravesical instillation prior to TUR (group B). The major side effects encountered were pollakisuria and miction pain, which occurred in 32% of the patients in group A and in 52% of those in group B.

Administration, Intravesical↗

Evaluation of systemic chemotherapy with methotrexate, vinblastine, adriamycin, and cisplatin for advanced bladder cancer. The Japanese Urological Cancer Research Group for Adriamycin.

In a cooperative study of the Japanese Urological Cancer Research Group for Adriamycin, the usefulness of chemotherapy with methotrexate, vinblastine, Adriamycin, and cisplatin (M-VAC therapy) in treating advanced or recurrent bladder cancer was examined. Evaluation of the clinical responses obtained in 86 evaluable patients revealed 13 complete responses, 29 partial responses, 4 minor responses, 19 cases of no change, and 21 cases of progressive disease. The overall response rate was 48.8% (42/86). The rate of response to M-VAC therapy at each disease site was as low as 21.4% (3/14) in bone lesions but exceeded 40% in the primary lesion, the lymph nodes, the lung, the liver, and other lesions. The clinical response to M-VAC therapy was not significantly influenced by the performance status of the patients, the dose intensity, or previous therapy. The median duration of response for the 42 responders was 22.7 weeks (range, 8.1-134.1 weeks), and the median duration of survival for the 86 evaluable patients was 9.8 months. Side effects were frequently encountered; the patients experienced anorexia, nausea, vomiting, malaise, alopecia, and leukopenia, but all of these symptoms were tolerable.

Adult↗

Selective and superselective infusion of urokinase for embolic stroke.

Intraarterial administration of urokinase using Tracker microcatheter was performed in 11 patients with acute cerebral infarction caused by embolic occlusion of the internal carotid or the middle cerebral artery. Recanalization was observed in seven cases (64%) following the fibrinolytic therapy, and the time until recanalization from the start of the treatment was on the average 2.8 hours. Recanalization was seen in five out of six cases that received superselective infusion of urokinase, while it was seen in two out of five cases that received selective infusion. This study suggests that superselective infusion of urokinase is an excellent therapeutic method for embolic occlusion of the cerebral artery.

Acute Disease↗

Spontaneous disappearance of a huge cerebral arteriovenous malformation: case report.

A case of spontaneous disappearance of a cerebral arteriovenous malformation (AVM) is reported. A 59-year-old woman, who had been diagnosed as having a huge AVM in the left occipital lobe 6 years before and who was monitored without treatment, complained of a sudden headache and vomiting. Computed tomography revealed an acute subdural hematoma, intracerebral hematoma, and subarachnoid hemorrhage, for which a craniotomy was performed. Cerebral angiograms performed 9 days after the operation demonstrated a decrease in the size of the AVM. Repeated cerebral angiograms performed a month later demonstrated complete disappearance of the AVM. Follow-up angiograms performed 19 months after hemorrhage confirmed complete disappearance of the AVM. Spontaneous disappearance is known to occur occasionally in small AVMs but rarely in huge ones such as the one presented here. Several possible mechanisms for spontaneous disappearance of AVMs are discussed.

Arteriosclerosis↗

[Results of deep dorsal vein ligation for venogenic impotence].

We treated seventy venogenic impotence with ligation of the deep dorsal vein of the penis. Their corporal veno-occlusive function was evaluated by dynamic infusion cavernosometry and cavernosography (DICC). Under local anesthesia, we made a longitudinal skin incision at the base of the penis. The deep dorsal vein was ligated and also a portion of this vein of 1.5 cm long was resected together with branches surrounding the vein. After the operation, the infusion rate determined by DICC was confirmed to be decreased in almost all patients. Thirty nine out of seventy cases had their erectile capability restored and reported that they could achieve sexual intercourse. Sixty one of the seventy cases showed full erection together with an intracavernous papaverine injection. However fifty percent of the sixty one patients who became capable of obtaining erection with the treatment had lost their erectile capability again within one year of the operation, however the other fifty percent were shown to maintain their erectile capability for up to three years. As four years after the treatment only thirty percent of those who had achieved the initial erectile capability still remained potent. This operation is easy to perform without any major complications, and its outcome is as good as that achieved by other more invasive venous ligation in the treatment of patients with venogenic impotence. We therefore conclude that penile deep dorsal vein ligation and partial resection of the vein one of the most useful treatments currently available for venogenic impotence and should be the treatment of choice.

Adult↗

[Double-blind trial of oral prostaglandin E1 on impotence].

The effect of oral prostaglandin E1 (limaprost) on erectile function was studied in a double-blind placebo controlled trial. Fifty one patients who agreed to participate were examined for their subjective symptoms and nocturnal erection was recorded using an erectometer at the beginning of the study, after an initial 6 week period, and again after a second 6 week period. Patients were randomly assigned to a group which received placebo followed by limaprost or to a group which received limaprost followed by placebo. Ten cases dropped out. In the remaining forty one patients, NPT during the limaprost phase was significantly different from that during the placebo phase. Patients with the history of diabetes mellitus, hypertension, or pelvic surgery showed relatively poor responses to oral prostaglandin E1. Oral prostaglandin E1 achieved 42.9% effectiveness in the psychogenic impotence, and this effectiveness is significantly higher than that of placebo. Oral prostaglandin E1 was suggested as an additional or alternative therapy in the management of psychogenic impotence. Psychogenic impotent who didn't respond to sex therapy and patients with slight organic causes would seem to benefit from oral prostaglandin treatment.

Administration, Oral↗

[A case of erythropoietin-producing renal cell carcinoma with a skin metastasis].

An 83-year-old man came to our hospital complaining of asymptomatic gross hematuria. We found a subcutaneous tumor in his chest and an abdominal mass in his left upper quadrant. Laboratory data showed red blood cell count of 737 x 10(4)/mm3 and hemoglobin level of 17.9 g/dl. The serum erythropoietin level measured by radioimmunoassay was considerably high. He underwent left nephrectomy and tumor resection in the chest wall. Serum erythropoietin level became normal following surgery and erythrocytosis disappeared. Histological findings revealed renal cell carcinoma, alveolar type, clear cell subtype, grade 2. The erythropoietin levels of the extracts of the cancer tissue and the normal kidney tissue were 2430 mU/g and 59.5 mU/g, respectively. Lung, liver and bone metastases appeared four months after the operation and serum erythropoietin level increased again.

Aged↗