Prediction of outcome in fulminant hepatic failure by serum human hepatocyte growth factor.
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Growth Substances↗
Biomedical subjects
S Kawakami
Publications and source records attributed to S Kawakami.
Effects of protein kinase inhibitors on the mitogenic activity of human hepatocyte growth factor on rat hepatocytes in primary culture.
To evaluate the role of protein phosphorylation reactions in signal transduction of human hepatocyte growth factor (hHGF), now known to be the same protein as the scatter factor and tumor cytotoxic factor, we examined the effects of various inhibitors of protein kinases on the mitogenic activity of hHGF on rat hepatocytes in primary culture. Genistein, a specific inhibitor of tyrosine kinase, dose-dependently inhibited the effect of hHGF in stimulating DNA synthesis of hepatocytes. By contrast, 1-(5-isoquinolinesulfonyl)-2- methylpiperazine (H7), a specific inhibitor of protein kinase C, potentiated the stimulatory effect of hHGF on DNA synthesis of hepatocytes. H7 was effective at over 2 micrograms/ml and potentiated the effect of hHGF over 2-fold at 20 micrograms/ml. On the other hand, an inhibitor of Ca++/calmodulin-dependent protein kinase inhibited both the basal and hHGF-stimulated DNA synthesis in the cells, whereas an inhibitor of cyclic nucleotide-dependent protein kinases had little effect on the action of hHGF. These results suggest that tyrosine phosphorylation is required for stimulation of hepatocyte DNA synthesis by hHGF and that the action of hHGF is negatively regulated by protein kinase C activation.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Identification and partial characterization of two classes of receptors for human hepatocyte growth factor on adult rat hepatocytes in primary culture.
To characterize the receptor(s) for human hepatocyte growth factor (hHGF), a physiological hepatotrophic factor involved in liver regeneration following hepatic injury, recombinant hHGF (rhHGF) was radioiodinated. The labeled rhHGF retained its full biological activity on adult rat hepatocytes in primary culture. The specific binding of [125I]iodo-rhHGF to hepatocytes reached a plateau within 240 min at 4 degrees C. Scatchard plot analysis of the binding data suggested the presence of two classes of high affinity binding sites for [125I]iodo-rhHGF. One of the sites had a dissociation constant (Kd) of about 4.6 pM with 300 sites/cell and the other has a Kd of about 275 pM with 15,160 sites/cell. Unlabeled rhHGF displaced cell surface-bound [125I]iodo-rhHGF in a dose-dependent manner as did native hHGF purified from plasma of patients with fulminant hepatic failure. However, other growth factors to rat hepatocytes in primary culture such as insulin and human epidermal growth factor, and proteins which have high amino acid sequence-homology to hHGF such as plasminogen and prothrombin, did not compete with [125I]iodo-rhHGF in the binding, which suggests the binding was specific to hHGF. Covalent cross-linking experiment of [125I]iodo-rhHGF to cell surface receptor(s) on hepatocytes showed there were two macromolecular species with apparent molecular weights of 330,000 and 230,000. Unlabeled rhHGF and native hHGF competed for the binding of [125I]iodo-rhHGF to the two macromolecular species, but insulin, human epidermal growth factor, plasminogen, and prothrombin did not. Based upon our estimated molecular weight of rhHGF = 84,000, these results suggest that hHGF specifically binds to two polypeptides of 246,000 and 146,000 daltons which are likely to represent the hHGF receptors of primary cultured rat hepatocytes.
Animals↗
The prognosis of patients with gastric cancer possessing sex hormone receptors.
Estrogen receptors (ER) and progesterone receptors (PgR) were immunohistologically investigated in 107 patients with gastric cancer who underwent curative resection. Both ER and PgR were detected only in the cancer cell nucleus. The ER positive rate was 27.7% for males and 31.0% for females, while the PgR positive rate was 9.2% for males and 11.9% for females. Clinicopathologically, the ER positive rate was slightly higher in young females and in cases of poorly differentiated gastric cancer. When cumulative survival rates were analyzed in relation to the presence or absence of receptors, the 10-year cumulative survival rate after surgery was significantly lower in the ER positive cases, being 15.7% cent, than in the ER negative cases, being 62.7%, and also significantly lower in the PgR positive cases, being 18.2%, than in the PgR negative cases, being 48.3%. The coexistence of ER and PgR in gastric cancer tissues suggests that the ER is physiologically active, or that ER positive gastric cancer is hormone-dependent. The poor prognosis of patients with receptor positive gastric cancer suggests that gastric cancer with these receptors is highly malignant.
Female↗
Sarcoidosis with tumorous hepatic and bone lesions mimicking disseminated malignancy: a case report.
An asymptomatic 49-year-old woman with a diffuse abnormal shadow detected on a routine chest rentogenogram was referred for evaluation. Ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) revealed space-occupying lesions in the liver and spleen. Lymphadenopathy was observed in the mediastinum and abdomen on CT, and multiple lesions of low signal intensity were observed in the spine on MRI. Furthermore, the presence of multiple tumorous nodules in the liver suggesting metastatic hepatic cancer was demonstrated on laparoscopy. Biopsy of the liver tumors revealed sarcoidosis; transbronchial biopsy specimens showed identical histological features. After administration of prednisolone for one month, the space-occupying lesions in the liver, spleen and spine improved. This case of sarcoidosis exhibited hepatic tumorous nodules and space-occupying lesions in the spleen and the spine which mimicked the presence of metastatic hepatic cancer.
Diagnosis, Differential↗
Rapid detection of the mecA gene in methicillin-resistant staphylococci by enzymatic detection of polymerase chain reaction products.
In order to identify methicillin-resistant staphylococci from clinical sources with ease and reliability, enzymatic detection of polymerase chain reaction (ED-PCR) was applied. ED-PCR is based on the capture of amplified products via biotin-streptavidin affinity and the detection of an incorporated hapten in amplified products with an enzyme-linked antibody. In order to identify methicillin-resistant staphylococci of all species, a 150-bp fragment of the mecA gene was targeted for ED-PCR. After PCR was performed with a pair of biotin and dinitrophenol 5'-labeled primers, the reaction mixture was applied to a microtiter well precoated with streptavidin. Thereafter, bound PCR products were detected colorimetrically with alkaline phosphatase-conjugated anti-dinitrophenol antibody. The extraction of DNA from staphylococcal cells for PCR was simplified so that it could be performed within one tube. The total assay, including PCR, took less than 3 h. The sensitivity of mecA gene detection ranged from greater than 5 x 10(2) CFU per tube for Staphylococcus aureus to greater than 5 x 10(3) CFU per tube for Staphylococcus epidermidis. Genotyping results obtained by ED-PCR of 161 tested strains from the colonies (97 strains of S. aureus and 64 strains of coagulase-negative staphylococci) were compared with the phenotypic susceptibilities of the strains to oxacillin. The results of ED-PCR showed excellent agreement with the MICs of oxacillin with very few exceptions; only one strain of S. aureus and two strains of coagulase-negative staphylococci were found to possess the mecA gene, which was discrepant with their phenotypes. Fifty-five blood culture samples were also tested by ED-PCR. For staphylococcal isolates in 33 of the cultures, oxacillin MICs were >4 microgram/ml; 31 of the 33 staphylococcal isolates were determined by ED-PCR to be mecA gene positive. These results suggest that ED-PCR can be used with reasonable confidence in the clinical microbiological laboratory.
Alkaline Phosphatase↗
Mechanical circulatory support with a centrifugal pump after open heart surgery.
Since December 1988, a centrifugal ventricular assist device (VAD) was used to support the circulation in 5 patients who could not be weaned from cardiopulmonary bypass (CPB) or developed cardiogenic shock after removal from CPB. Three patients required a left VAD, one needed a right VAD. One patient had biventricular support using a centrifugal left VAD and a diaphragm type right VAD. The duration of the centrifugal VAD support ranged from 6 to 136 (mean 72)h. All patients were weaned from the VAD, but only 2 patients were discharged from the hospital. Two patients died of multiple organ failure, and one died of cardiogenic shock caused by intractable arrhythmia. Infection occurred in all non-survivors, and 2 of them developed renal failure. We conclude that the centrifugal VAD is effective to recover a failing ventricle. The factors related to the unsuccessful recovery were delayed start of the VAD support and major complications such as infection as infection and renal failure.
Adult↗
[Primary carcinoma in situ of the ureter: a case report].
A 47-year-old man presented with gross hematuria and left lower abdominal dull pain of 6-weeks duration. Cystoscopic examination revealed bloody efflux from the left ureteral orifice but no tumor in the bladder. Retrograde pyelogram showed irregular stricture of middle portion of the left ureter. Cytologic studies of the voided urine and left ureteral urine were positive for cancer, and nephro-ureterectomy with excision of a bladder cuff was carried out. The surgical specimen showed no intraluminal mass but histologically, transitional cell carcinoma in situ with G3 anaplasia and squamous metaplasia was found in the narrowed portion of the ureter. Followup examinations, including exfoliative urinary cytology, cystoscopy and IVP revealed no abnormalities until intravesical recurrence was confirmed 34 months later. Transurethral resection of bladder tumor was performed and superficial papillary transitional cell carcinoma with G2 anaplasia was found in the trigone of the bladder. Followup examinations for the last one year have revealed no abnormalities.
Carcinoma in Situ↗
[Two cases of thyroid metastases from renal cell carcinoma].
The identification and diagnosis of thyroid metastases from renal cell carcinoma are rare in living patients in spite of more frequent incidence during autopsy. We reported two cases of thyroid metastases from renal cell carcinoma. In both cases, histological examination revealed metastasis from renal cell carcinoma and negative immunohistological stain for thyroglobulin ruled out primary thyroid carcinoma.
Carcinoma, Renal Cell↗
[Clinical efficacy of tosufloxacin on the patients with urinary tract infections].
We evaluated a newly developed quinolone agent, tosurofloxacin (TFLX), for its safety and clinical efficacy on patients with urinary tract infections (UTI). Among 138 cases satisfying the UTI criteria, 75 cases were acute simple UTI and 63 cases were chronic complicated UTI. In principle, a daily dose of 450 mg of TFLX was administered for 3 days and for 5 days for acute simple UTI and for chronic complicated UTI, respectively. Clinical efficacy of TFLX in these cases was evaluated according to the criteria of Japanese UTI committee. Bacteriologically, all 80 strains isolated from acute simple UTI were eradicated following TFLX administration. However, 2 gram positive strains and 1 gram negative strain, appeared following the treatment. In cases of chronic complicated UTI, 29 out of 32 gram positive strains and 29 out of 44 gram negative strains were eradicated. Among the isolated strains, P. aeruginosa and S. marcescens persisted, which suggests that they were less sensitive to TFLX. Overall clinical effectiveness rate of TFLX on acute simple UTI was 100%, while that on chronic complicated UTI was 73%. Adverse drug side effects were minimum, stomach discomfort and constipation was observed in one case each. These findings indicate that TFLX is a useful agent for the treatment of both simple and complicated UTI.
4-Quinolones↗
[Enterovesical fistula complicating Crohn's disease: report of two cases].
Two female patients with enterovesical fistula complicating Crohn's disease are presented. Case 1: A 40-year-old woman having a 10-year history of diarrhea presented with vesical irritability of a three months duration. Administration of antibiotics did not relieve her of the symptoms and then pneumaturia appeared. Cystoscopic examination revealed fistulous opening. Barium enema study depicted rectovesical fistula. After partial cystectomy and temporary colostomy, ileocecal lesion was shown by contrast study and resection of ileocecal segment was performed seven months later. Case 2: A 33-year-old woman presented with vesical irritability of 7 years duration and pneumaturia and fecaluria of 4 years duration. Cystoscopic examination revealed localized bullous edema but no apparent fistula. Cystography, as well as contrast studies demonstrated ileo-vesical, ileo-ascending colonic and ileo-sigmoidal fistulas. One-stage resection of diseased intestine and partial cystectomy were performed. In both cases, pathological diagnoses of Crohn's disease was made, and postoperative course was uneventful for over 10 months. Thirty eight cases of enterovesical fistula complicating Crohn's disease are reviewed.
Adult↗
[Adrenal pseudocyst: a case report].
A 23-year-old man presented with high fever and left abdominal pain. Ultrasonography, CT scan and angiography visualized a left adrenal cyst. Cyst fluid obtained preoperatively by percutaneous needle puncture under ultrasonographic guidance was purulent, and had a higher level of aldosterone, and lower level of amylase than the plasma. These findings suggested that this cyst originated from the adrenal gland. Histopathological examination of the surgically removed specimen confirmed the adrenal pseudocyst.
Adrenal Gland Diseases↗
Localization of estrogen receptors in gastric cancer using immunohistochemical staining of monoclonal antibody.
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Adult↗
Human hepatocyte growth factor in blood of patients with fulminant hepatic failure. I. Clinical aspects.
The levels of human hepatocyte growth factor (hHGF) in sera obtained from patients with various liver diseases were determined using adult rat hepatocytes maintained in primary culture. The mean hHGF activity for 22 patients with fulminant hepatic failure was about nine times greater than that found in normal human serum. The increase in serum hHGF activity seen in two patients with "acute-on-chronic" hepatitis was similar to that found in patients with fulminant hepatic failure. The serum level of hHGF from patients with acute hepatitis is related to the stage of their illness. The average value for 31 patients was about three times that of normal human serum. In some patients, the time course for the increase in serum hHGF activity was similar to that demonstrated for alpha-fetoprotein. The mean hHGF activity in serum for the 33 patients with chronic hepatitis and from 25 patients with liver cirrhosis was increased also compared with that of normal human serum. In addition, serum hHGF activity in three of seven patients studied after partial hepatectomy for a space-occupying lesion of the liver was increased. These data suggest that the increase in serum hHGF activity present in patients with various liver diseases reflects a self-defense mechanism that is involved in the process of liver cell regeneration.
Growth Substances↗
Application of transrectal ultrasonography in modified Stamey procedure for stress urinary incontinence.
From June 1989 to August 1990, 21 women with genuine stress urinary incontinence were treated with the Gittes procedure combined with transrectal ultrasonography. The urethrovesical junction was well pinpointed on an ultrasonographic image. The strength of suspension providing the optimal posterior urethrovesical angle was changed by each patient. Posterior urethrovesical angles averaged 89.3 +/- 9.5 degrees at operation and 93.6 +/- 9.5 degrees (mean +/- standard deviation) on a postoperative lateral cystourethrogram with the patient straining while in the standing position. An indwelling urethral catheter was removed on postoperative day 1. None of the patients had residual urine of more than 50 ml. by 4 days postoperatively. Furthermore, the average maximum urinary flow rates significantly increased from 21.0 +/- 7.1 ml. per second preoperatively to 26.1 +/- 9.8 ml. per second postoperatively (p less than 0.01). Therefore, application of ultrasonography during bladder neck suspension is simple and reliable for determination of the optimal suspension as well as identification of the suspension site.
Adult↗
Successful use of the centrifugal ventricular assist device for postcardiotomy cardiogenic shock.
A centrifugal pump was successfully used as a left ventricular assist device (LVAD) in a 54-year-old female who developed cardiogenic shock following open heart surgery. Cardiac index prior to the LVAD support was 1.4 l/min/m2 and increased to 3.0 l/min/m2 at removal of the device, which assisted for 88h. She resumed her daily activity 10 months after the operation and is in New York Heart Association functional class I.
Cardiac Surgical Procedures↗
Levels of the human hepatocyte growth factor in serum of patients with various liver diseases determined by an enzyme-linked immunosorbent assay.
We have found a hepatotrophic factor in plasma or sera of patients with fulminant hepatic failure and have purified human hepatocyte growth factor from plasma of these patients. In this study we developed an enzyme-linked immunosorbent assay with high specificity and sensitivity for human hepatocyte growth factor in human serum. This assay for serum human hepatocyte growth factor is a sandwich method consisting of three steps. The standard curve for human hepatocyte growth factor appeared to be linear in the range of 0.20 to 12.50 ng purified human hepatocyte growth factor/ml (2.35 to 147 pmol/L). The assay took about 4 hr. Serum human hepatocyte growth factor values in patients with fulminant hepatic failure measured by enzyme-linked immunosorbent assay showed a strong positive correlation with that by bioassay using rat hepatocytes in primary culture. The mean value of serum human hepatocyte growth factor for 30 normal subjects was 0.24 +/- 0.12 (S.D.) ng/ml; that for 23 patients with fulminant hepatic failure was 8.06 +/- 1.76 (S.E.M.) ng/ml- greater than 30 times greater than the mean value for normal subjects. Serum human hepatocyte growth factor levels in patients with acute hepatitis, chronic hepatitis and cirrhosis were found to be slightly higher than those in normal subjects, but only the increase in serum human hepatocyte growth factor of acute hepatitis patients was statistically significant. The enzyme-linked immunosorbent assay for serum human hepatocyte growth factor should prove useful for serum human hepatocyte growth factor level measurement in patients with various liver diseases.
Enzyme-Linked Immunosorbent Assay↗
[Retention cyst of the prostate with projection of hyperplastic tissue: report of a case].
A 46-year-old man presented at Kasukabe City Hospital because of urinary retention. Digital rectal examination revealed soft distended mass in the retrovesical space. Transrectal ultrasonography and computed tomography showed a retrovesical cystic lesion of 14 x 11 x 10 cm in size and a mass protruding into the cyst from posterior lobe of the prostate. The cyst and the mass were removed suprapubically. The cyst was filled with 400 ml of clear yellowish fluid containing acid-phosphatase and prostate-specific antigen in a high concentration, but no spermatozoa. The mass protruded posteriorily from the prostate. The wall of the cyst was partly lined with double layer of columnar epithelium. The histological examination of the mass showed marked nodular hyperplasia and dilated acini of the prostate gland was seen around the cyst. A diagnosis of retention cyst of the prostate and nodular hyperplasia of the prostate were made. Cysts of the prostate are uncommon and retention cysts protruded by markedly hyperplastic prostatic tissue are extremely rare.
Cysts↗