PubMed HealthSearch

Biomedical subjects

S Kitada

Publications and source records attributed to S Kitada.

At least 19 recordsLinked to original sources

The content of urokinase-type plasminogen activator antigen as a prognostic factor in urinary bladder cancer.

Urokinase-type plasminogen activator (u-PA) is thought to be implicated in cancer invasion and metastasis. The aim of this study was to determine whether the u-PA content of cancer tissue is a prognostic factor in bladder cancer. Tissue samples from 46 patients with bladder cancer were assessed for u-PA antigen by a highly sensitive enzyme immunoassay. The relationships between the u-PA level in extracts of bladder cancer and the survival rates of the bladder-cancer patients were examined. Patients with a high u-PA level (8 ng/mg of protein and more) showed a statistically significantly higher rate of survival than those with a low u-PA level (p less than 0.005). The u-PA antigen level in cancer tissue was significantly lower in low-graded and non-invasive cancers than in others (p less than 0.01).

Aged

The relationship between cardiovascular complications of estrogen therapy and fibrinolysis in patients with prostatic cancer.

To determine the relationship between cardiovascular complications of estrogen therapy and fibrinolysis, fibrinolysis parameters plasminogen, urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1), were assessed in 12 prostatic cancer patients before and 6 weeks after the onset of estrogen therapy. The levels of plasminogen, u-PA, and PAI-1 in the patients treated with the estrogen therapy were significantly higher than those in the patients before the therapy. The t-PA level in the patients during the therapy was significantly lower than that before the treatment. Cardiovascular complications were found in two patients (16.7%) during estrogen therapy. In the two patients, marked elevation of PAI-1 and decreased level of t-PA were observed during the therapy. These results indicate that cardiovascular complications of estrogen therapy in patients with prostatic cancer may be related to hypofibrinolysis resulting from changes of PAI-1 and t-PA.

Aged

Molecular evolution of human paramyxoviruses. Nucleotide sequence analyses of the human parainfluenza type 1 virus NP and M protein genes and construction of phylogenetic trees for all the human paramyxoviruses.

The nucleotide sequences of the NP and M genes of human parainfluenza type 1 virus (HPIV-1) were determined. The NP gene was 1677 nucleotides long excluding polyadenylic acid. The NP gene contained a single large open reading frame (ORF), which encoded a polypeptide of 524 amino acids with a calculated molecular weight of 57,736. The M gene 1173 nucleotides long excluding the poly(A) tract and the sequence also contained a single large ORF which encoded a polypeptide of 348 amino acid with a molecular weight of 38,445, which was inconsistent with 28 kDa previously determined by SDS-PAGE. We aligned the deduced HPIV-1 NP and M protein sequences with 12 and 13 other paramyxoviruses, respectively, suggesting that a common tertiary structure was found in the NPs or Ms of HPIV-1, Sendai virus (SV), HPIV-3 and BPIV-3 and that other common structure was also maintained in these proteins of HPIV-2, SV 41 and 5, MuV, HPIV-4. Phylogenetic trees were constructed for the NP and M proteins of all the paramyxoviruses of which nucleotide sequences had been previously reported. Paramyxoviruses could be subdivided into two groups, i.e., PIV-1 group and PIV-2 group; the former group is composed of HPIV-1, SV, HPIV-3 and BPIV-3, and the latter group consists of HPIV-2, SV 41, SV 5, MuV, HPIV-4 A and HPIV-4 B.

Amino Acid Sequence

The prognostic significance of vascular invasion in upper urinary tract transitional cell carcinoma.

The prognostic significance of vascular invasion was evaluated in a retrospective series of 30 patients with upper urinary tract cancer who underwent a potentially curative operation. Vascular invasion was found in 11 patients (36.7%). The incidence of vascular invasion was well correlated with tumor grade and stage. The incidence of metastases postoperatively was significantly higher in the patients with (72.7%) than without (21.1%) vascular invasion (p < 0.01). The survival rate of the patients with vascular invasion was significantly lower than in those without vascular invasion (p < 0.005). In multivariate Cox regression analysis the prognostic value of vascular invasion was independent of tumor stage and grade. These results indicate that vascular invasion should predict a more unfavorable outcome in patients with upper urinary tract cancer as an independent morphological indicator.

Adult

Bladder function in elderly men with subclinical brain magnetic resonance imaging lesions.

Among 43 men more than 60 years old who complained of urinary irritative symptoms 40 had subclinical lesions in the brain on magnetic resonance imaging (MRI). Of these 40 patients 23 (57.5%) had detrusor hyperreflexia. The mean age of the patients with and without detrusor hyperreflexia was 75.8 and 68.2 years, respectively, which is a statistically significant difference. Patients with detrusor hyperreflexia were more likely to have lesions of the basal ganglia than patients without detrusor hyperreflexia. This study suggests that detrusor hyperreflexia, subclinical MRI lesions in the brain and aging are intimately interrelated.

Aged

The effects of transferrin receptor antibody, transferrin receptor antibody bound to Pseudomonas exotoxin and transforming growth factor-alpha bound to Pseudomonas exotoxin on human tenon's capsule fibroblast proliferation.

Pharmacological agents which modulate the wound healing process by the inhibition of proliferation of fibroblasts may improve the success of glaucoma filtration surgery. Since cell proliferation is essential to the wound healing process, we targeted the surface receptors that are associated with proliferating cells. We present the effects of three such agents-purified mouse anti-human transferrin receptor monoclonal antibody 42/6 (anti-TfR-42/6), anti-transferrin monoclonal antibody bound to a Pseudomonas exotoxin (anti-TfR-PE40) and transforming growth factor-alpha Pseudomonas exotoxin (TGF-alpha-PE40)--on human fibroblasts from Tenon's capsule. The inhibition of human subconjunctival fibroblast proliferation by anti-TfR-42/6 (with a concentration up to 25 micrograms/ml) and by anti-TfR-PE40 and TGF-alpha-PE40 (both with a concentration range of 5000-0.00001 micrograms/ml) was determined by colorimetric (OD), and cell counting (CC) assays over a 9-day period. Neither anti-TfR-42/6 nor anti-TfR-PE40 had an antiproliferative effect on the fibroblasts. TGF-alpha-PE40 demonstrated an antiproliferative effect in a dose response manner. The mean 50% inhibitory dose (ID50) by OD was 32.91 micrograms/ml, while the ID50 by CC was 27.88 micrograms/ml. EGF was used as a negative control for TGF-alpha-PE40 toxin. The inhibitory effect of the toxin conjugate was completely blocked by the addition of 1000 micrograms/ml of EGF. These in vitro studies show that TGF-alpha-PE40 may be useful in modulating the proliferation of human ocular fibroblasts; they also give some indication of drug dosages for future in vivo testing.

ADP Ribose Transferases

[Studies on vessel invasion by cancer of the renal pelvis and ureter].

The significance of vessel invasion by cancer of the renal pelvis and ureter was estimated with surgical specimens of 45 patients. The vessel invasion by cancer was observed in 25 out of 45 cases (55.6%). The incidence of vessel invasion increased with the grade of cancer and the extent of the primary tumor. The postoperative metastases by cancer was noted in 22 of the 25 patients with vessel invasion (88%) and in 4 of 20 (20%) patients without vessel invasion. The incidence of metastases in patients with vessel invasion was significantly higher than that without it (p < 0.01). The 5-year survival rate was 13.1% in the patients with vessel invasion and 80.6% in the patients without it (p < 0.005). Postoperative chemotherapy had no effect on the unfavorable outcome of the patients with vessel invasion. Therefore, vessel invasion by cancer may be one of the prognostic factors in renal pelvic and ureteral cancer. The patients with vessel invasion should be treated with more aggressive therapy to improve the poor prognosis.

Adult

[Clinical significance of urinary flow pattern--based on combined uroflowmetry and external sphincter electromyography].

We performed combined uroflowmetry and external sphincter electromyography in 108 patients (87 males and 21 females); 16 serving as normal controls, 49 with benign prostatic hyperplasia, 16 with overactive type of neurogenic bladder, 27 with underactive type of neurogenic bladder. Urinary flow pattern was classified into 5 categories. All of urinary flow patterns of normal controls showed pattern A which had the form of a bell. EMG showed complete suppression during micturition followed by a few intermittent increases in amplitude. Urinary flow patterns of BPH patients were distributed widely from pattern A to E. Intermittent increases in EMG amplitude during a late phase of micturition were characteristic in patients with BPH. We must pay attention to sex differences to evaluate urinary flow pattern because it could be influenced by abdominal pressure such as stressing or Créde maneuver in female patients with an underactive type of neurogenic bladder.

Adult

[The effects of autonomic agonists on the female rabbits urethra--in vitro isovolumetric and isometric study].

To investigate the characteristics of adrenoceptors of the proximal urethra in female rabbits, we performed the in vitro isovolumetric urethral pressure study and isometric study with three parts of muscle strips of the proximal urethra (whole layers, inner layers and outer layers). Both alpha-1 and alpha-2 agonist caused dose dependent response in in vitro isovolumetric pressure study as well as in vivo study. However, the response of alpha-2 agonist in in vitro was small in magnitude compared to in vivo study, suggesting the influence of permeability of drugs from serosa to mucosa in in vitro whole urethra study. The response of the strips of inner layers to alpha-1 agonist is almost the same as that of outer layers and whole layers, while the response of inner layers to alpha-2 agonist is almost twice as that of other layers. These findings are suggestive of predominance of alpha-2 adrenoceptors mediating contractions in the inner layers of the proximal urethra in female rabbits. Alpha-2 adrenoceptors which probably are distributed in mucosal and submucosal layers may have an important role in the mechanism of urinary continence in female rabbits.

Adrenergic alpha-Agonists

Effects of timolol, betaxolol, and levobunolol on human tenon's fibroblasts in tissue culture.

Evidence has been found suggesting that long-term therapy with topical antiglaucoma medications may decrease the success of glaucoma filtering surgery. To investigate this question further, the antiproliferative effects of the preservative benzalkonium chloride and three pure and commercially available beta-adrenergic antagonist preparations (timolol, betaxolol, and levobunolol) were studied on tissue cultures of human Tenon's capsule fibroblasts. Each drug preparation was tested on three different cell lines. Fibroblast growth was measured with tritiated thymidine uptake and hexosaminidase assays. Trypan blue uptake was used to assess cell viability microscopically. The commercially available preparations containing benzalkonium chloride and those of betaxolol and levobunolol without the preservative had similar inhibitory doses for 50% of cells. The timolol preparation without preservative was significantly less toxic than its commercially available one. The three tested beta-adrenergic blockers did not stimulate fibroblast proliferation directly in this in vitro model. Even when the cultures were washed free of the drugs, growth continued to be suppressed, suggesting that the inhibition was not reversible. An increase in fibroblasts and inflammatory cells after long-term antiglaucoma medical therapy thus may be caused not by a direct stimulation of cell proliferation but by chronic inflammation from the irritating effects of antiglaucoma medications and/or their preservatives.

Benzalkonium Compounds

Comparative immunohistochemistry of malignant fibrous histiocytoma and sarcomatoid carcinoma of the urinary tract.

An immunohistochemical analysis using antibodies to cytokeratin, epithelial membrane antigen, alpha-1-antitrypsin, alpha-1-antichymotrypsin and factor XIIIa was performed in four cases of malignant fibrous histiocytoma and five cases of sarcomatoid carcinoma in the urinary tract. All cases of malignant fibrous histiocytoma showed positive staining for factor XIIIa, alpha-1-antitrypsin and alpha-1-antichymotrypsin. No case was positive for factor XIIIa, but one case with sarcomatoid carcinoma stained positive for alpha-1-antitrypsin and alpha-1-antichymotrypsin. All cases showed positive staining for cytokeratin and 4 cases with sarcomatoid carcinoma were positive for epithelial membrane antigen, but no cases with malignant fibrous histiocytoma were positive. Immunohistochemical analysis would thus help to distinguish malignant fibrous histiocytoma from sarcomatoid carcinoma of the urinary tract.

Aged

Inhibition of rabbit ocular fibroblast proliferation by 5-fluorouracil and cytosine arabinoside.

Inhibition of rabbit subconjunctival fibroblast attachment and proliferation by the antimetabolites 5-fluorouracil (5-FU) and cytosine arabinoside (ara-C) was determined by radionucleotide uptake, cell counting, and colorimetric assays for the concentration range of 1000 to 0.0001 micrograms/ml over an 11-day period. The mean 50% inhibitory doses (ID50s) against proliferation were calculated for each assay. Rabbit fibroblast attachment was not inhibited at any drug concentration by either 5-FU or ara-C. Ara-C was a 10 to 100 times more potent inhibitor of rabbit fibroblast proliferation than 5-FU. The mean ID50s for rabbit subconjunctival fibroblasts were compared with the mean ID50s from a similar series of experiments conducted in our laboratory on human subconjunctival fibroblasts. Unpaired t-test analysis showed a significant difference between the inhibitory effects of 5-FU on rabbit and human fibroblast proliferation. An ID50 against rabbit fibroblasts was detectable after 24 hours of incubation with 5-FU by the 3H-thymidine uptake assay, whereas the ID50 against human fibroblasts was detectable after 48 hours of incubation. Once inhibition of proliferation occurred, however, human fibroblasts were up to six times more sensitive to the antiproliferative effects of 5-FU than rabbit fibroblasts as measured by the 3H-thymidine uptake assay (p = 0.0005). Unpaired t-test analysis showed no statistical difference between the ID50s of ara-C on rabbit and human fibroblasts. Starting on day 3, however, doses greater than 1 micrograms/ml of ara-C were cytotoxic to rabbit fibroblasts but only cytostatic to human fibroblasts as determined by trypan blue uptake assay microscopically. Rabbit ocular fibroblasts may be useful in modelling the proliferation of human ocular fibroblasts in vitro to a limited degree. This tissue culture system may be useful for predicting optimal drug dosages for in vivo rabbit and human glaucoma filtering surgery.

Animals

Molecular relationships between human parainfluenza virus type 2, and simian viruses 41 and 5: determination of nucleoprotein gene sequences of simian viruses 41 and 5.

The nucleotide sequences of cDNAs of the simian virus 5 (SV5) nucleoprotein (NP) gene, and the 3' end of the genome and NP gene of SV41 were determined. The open reading frames of the SV5 and SV41 NP genes encode polypeptides with Mrs of 56,582 and 60,575, respectively, values which are consistent with those estimated by SDS-PAGE. The NP of human parainfluenza virus type 2 (hPIV-2) was more closely related to that of SV41 (amino acid sequence identity 70.5%) than that of SV5 (57.0%); the amino acid sequence identity between the NPs of SV41 and SV5 was 63.3%. The sequence of the 3' end of the genome of SV41 showed a high level of similarity to that of hPIV-2, the terminal 18 nucleotides being identical. It is concluded from these findings that SV41 is related most closely to hPIV-2, even though SV5 had been thought to be an animal type of hPIV-2.

Amino Acid Sequence

Experimental hyperreflexia: effect of intravesical administration of various agents.

In anesthetized rabbits, we can induce a significant degree of spontaneous activity in the urinary bladder by placing a ligature around the proximal portion of the external urethra. Previous studies characterized the activity as primarily reflex in nature, since intravesical hexamethonium selectively inhibited the hyperreflexia. In this current study we determined the effect of intravesical administration of a variety of compounds to inhibit the induced hyperreflexia. The following agents were tested at concentrations of 1, 10, 100 and 500 mumol/l (intravesically): verapamil, cromakalim, nifedipine, diltiazem, and atropine; lidocaine was tested in 0.05, 0.5 and 5% solutions. The results are summarized as follows: (1) Lidocaine was the most effective agent tested, virtually eliminating both the amplitude and frequency of the spontaneous activity at the lowest concentration (0.5%). (2) Verapamil and nifedipine were somewhat more potent than cromakalim and diltiazem. Atropine sulfate was the least potent, inhibiting both the amplitude and frequency of the hyperreflexia by less than 50% at 500 mumol/l. (3) In all cases, the amplitude of the spontaneous activity was inhibited to a significantly greater degree than the frequency of the spontaneous activity. (4) In general, there was no effect of any of the agents on mean arterial pressure at 1 or 10 mumol/l. At 100 and 500 mumol/l, all agents except for lidocaine and cromakalim decreased arterial pressure. These two agents produced no consistent fall in blood pressure at any concentration. In conclusion, the acute hyperreflexic (rabbit) preparation provides a highly reproducible and consistent model for the study of the effect of drugs on hyperreflexia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Chromosomal anomalies in cryptorchidism and hypospadias.

We have studied peripheral blood samples for chromosomal anomalies in 110 consecutive patients who had cryptorchidism and/or hypospadias. Of the patients 7 (6.4%) were found to have chromosomal anomalies. The incidence of chromosomal anomalies in patients with cryptorchidism only was 4/83 (4.8%), in patients with hypospadias only the incidence was 1/18 (5.6%) and in concomitant cases the incidence was 2/9 (22.2%). Of 69 patients with cryptorchidism and/or hypospadias who did not have any other congenital abnormalities, 3 patients (4.3%) were found to have sex chromosomal anomalies. However, of 41 patients associated with generalized congenital abnormalities including mental and growth retardation, we found 4 patients (9.8%) with autosomal anomalies. We conclude that most children with multiple associated abnormalities other than cryptorchidism and/or hypospadias should have chromosome analysis. Moreover, attention should be paid to sex chromosomal anomalies, even when patients with cryptorchidism and/or hypospadias do not have any associated generalized physical abnormalities.

Adolescent

Characterization of human and rabbit pigmented and nonpigmented ciliary body epithelium.

Nonpigmented epithelial (NPE) and pigmented epithelial (PE) cells were carefully dissected from both human and rabbit ciliary processes and have been maintained in vitro and partially characterized by morphology and immunocytochemical techniques using polyclonal and monoclonal antibodies against S-100 proteins, collagen type I and type III. The tissue distribution of these proteins was studied in formalin fixed deparaffinized tissue sections of human and rabbit eyes by immunoperoxidase staining techniques. Both NPE and PE cell lines from human and rabbit showed hexagonal morphology by light microscopy; distinct granules containing pigment could be visualized in the PE cell lines, but not in the NPE cells. Antibodies against S-100 proteins stained NPE layer intensely and PE layer slightly in the human tissue sections. The staining was less intense in rabbit tissues than human tissues. The ciliary body stroma was positive for collagen type III and negative for collagen type I or S-100.

Animals

The effects of the fluorinated pyrimidines FUR, FUdR, FUMP, and FdUMP on human Tenon's fibroblasts.

5-Fluorouracil (5-FU) has effectively inhibited fibroblast proliferation to prevent scar formation and bleb failure after glaucoma filtering surgery. To identify more potent but less toxic antiproliferative drugs, the authors studied cell attachment and proliferation of 5-FU metabolites: 5-fluorouridine (FUR), 5-fluorodeoxyuridine (FUdR), 5-fluorouridine-5'-monophosphate (FUMP), and 5-fluorodeoxyuridine-5'-monophosphate (FdUMP) on human Tenon's fibroblasts in vitro.

Adenosine