Autopsy findings of primary Sjögren's syndrome with end-stage renal failure.
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Female↗
Biomedical subjects
S Kubo
Publications and source records attributed to S Kubo.
Enhancement of superoxide production of polymorphonuclear neutrophils by ofloxacin and the effects of the inhibitors of protein kinase C.
Polymorphonuclear neutrophils (PMN) represent an important defense mechanism against bacterial infection. Superoxide is one of the most important factors released by PMN following various stimulations including bacteria. Augmentation of chemiluminescence response of PMN stimulated by phorbol myristate acetate was observed following the addition of 25-200 micrograms/ml of ofloxacin, a new quinolone antimicrobial agent. In addition, the effects of two inhibitors of protein kinase C, staurosporine and H-7, were examined. The augmented superoxide production was inhibited by 1 or 2 microM of staurosporine or 50 or 100 microM of H-7. These results suggest that ofloxacin augments superoxide production of PMN and that this augmentation is probably due to the enhancement of leukocyte protein kinase C.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Suppression of chemotactic activity of neutrophils in hyperosmotic conditions comparable to the renal medulla: partial preservation by phosphoenolpyruvate.
Chemotaxis is one of the most important functions of the polymorphonuclear leukocyte (PMN). In the host defense against pyelonephritis, the renal medulla is a site of interaction between bacteria and PMNs. At this site the osmotic pressure is elevated due to a high concentration of NaCl and urea. We evaluated the in vitro chemotactic activity of PMNs under the hyperosmolar conditions created by high concentrations of NaCl and urea. This activity was suppressed by the stimulation of opsonized zymosan and formyl-methionyl-leucyl-phenylalanine. The inhibition of chemotaxis was partially preserved by phosphoenolpyruvic acid (PEP), a precursor of adenosine triphosphate (ATP), in hyperosmolar NaCl but not in urea. The intracellular content of ATP was increased by supplementing the hyperosmolar NaCl with PEP. These observations suggest that inhibition of the chemotactic activity of PMNs is due to differing mechanisms for each NaCl and urea, and that PEP may protect the PMNs against hyperosmolar NaCl by maintaining ATP content.
Adenosine Triphosphate↗
Effect of recombinant human granulocyte-colony-stimulating factor on renal scarring following infection with MS-piliated bacteria.
Renal scars have been thought to occur only in later stages of chronic pyelonephritis. In our experimental pyelonephritis model, bacteria with mannose-sensitive (MS) pili on its surface promoted renal scarring when inoculated into renal parenchyma. Pretreatment with recombinant human granulocyte-colony-stimulating factor (rhGCSF) inhibited the renal scarring which followed inoculation with MS-piliated bacteria, whereas posttreatment at an early stage of infection had no effect on renal scarring. These findings suggest that rhGCSF may be useful for the prevention of infection without increasing the tissue damage to the renal parenchyma which leads to the renal scarring. Even when rhGCSF is used for treatment of kidney infection, it does not promote increased renal scarring through the increased invasion of leukocytes at the inflammatory site.
Animals↗
Suppressive effect of sera from patients undergoing chronic hemodialysis on neutrophil chemiluminescence response.
To determine the mechanism of easy infectability of uremic patients, we studied the effect of sera from uremic patients who were undergoing chronic hemodialysis on the chemiluminescence (CL) response of polymorphonuclear leukocytes (PMN). The luminol-dependent CL response was examined following stimulation with phorbol myristate acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (FMLP). The patient's sera suppressed the CL response following stimulation by PMA, but not by FMLP. These findings suggest that sera from uremic patients undergoing hemodialysis contain a suppressive substance that suppresses the activation of PMNs by PMA.
Female↗
Effect of prednisolone on renal scarring in rats following infection with Serratia marcescens.
Renal scarring is considered a criterion of reflux nephropathy and the end stage of pyelonephritis. Prednisolone, a strong anti-inflammatory drug, at doses of 1 or 2 mg/kg prevented renal scarring in rats following infection with Serratia marcescens. Four or 8 mg/kg of prednisolone, however, did not inhibit renal scar formation. In a time course experiment, renal scarring was prevented when 4-day treatment with prednisolone was initiated 2, 5, or 13 days after infection. These results show that prednisolone is effective in preventing such scarring and suggest the clinical use of this drug for preventing renal scar formation after pyelonephritis and reflux nephropathy.
Animals↗
Therapeutic effects of simultaneous use of glucose and insulin in ketotic dairy cows.
A glucose tolerance test was carried out on 8 ketotic dairy cows and 5 healthy dairy cows after injection of 500 ml of 50% glucose solution into the jugular vein. The blood insulin concentration increased from 6.3 microU/ml before glucose injection to 62.5 microU/ml after injection in the healthy group and from 3.0 to 22.9 microU/ml in the ketotic group. Insulin concentration before glucose injection was lower, and its increase after glucose injection was smaller, in the ketotic group. Five hundred milliliters of 50% glucose solution were administered to 15 ketotic cows by intravenous infusion once daily from d 1 to 6, and 200 U of insulin were injected subcutaneously in 8 of these cows from d 2 to 6. In the group administered insulin with glucose, the blood glucose concentration, insulin concentration, and insulin to glucagon ratio (50.5 mg/dl, 6.2 microU/ml, and .09, respectively) on d 6 were significantly higher than those for cows administered glucose only (36.3 mg/dl, 3.0 microU/ml, and .04, respectively). Also, the blood ketone bodies and free fatty acid concentrations on d 6 were significantly lower in the group receiving glucose plus insulin (22.1 microU/ml and .79 meq/L, respectively) than in the group receiving glucose alone (63.8 microU/ml and .98 meq/L, respectively). Thus, the simultaneous use of glucose and insulin is considered to be useful for the treatment of ketosis in dairy cows.
Animals↗
Immune factors correlating with improved long-term graft outcome in kidney, lung, and heart transplants.
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Bronchiolitis Obliterans↗
[Paternity test by DNA fingerprinting in a sexual assault].
We have applied the method of DNA fingerprinting to resolve a paternity case. DNA samples were extracted from the blood of mother, child (4 months old fetus) and alleged father, digested with the restriction endonuclease Hinf I and Hae III, size separated by agarose gel electrophoresis, and hybridized with the multi-locus minisatellite probe B.E.S.T.-MZ1.3 digoxigenin. DNA fingerprinting patterns in the child and alleged father indicated possibly paternity. Following extraction of DNA from cord blood (infant of 26 to 39 week's gestation), the quantity of DNA isolated was determined on a spectrophotometer at 260 nm and its integrity by electrophoresis in agarose gels. We found that high-molecular-weight DNA could be recovered in large quantities from cord blood as well as from adult blood.
DNA↗
[Indication and limitation of hepatectomy for hepatocellular carcinoma].
Hepatectomy for hepatocellular carcinoma (HCC) has become safer with recent advances in diagnostic methods, operative techniques and understanding of how to evaluate liver function. Hepatectomy is the treatment of choice for HCC provided that patients are selected carefully, because cure is possible with hepatectomy (some patients survive long without recurrence). However, the rate of recurrence after hepatectomy is high. Recurrences can arise because of either intrahepatic dissemination or factors that give rise to multicentric carcinoma, so one must decide the operative method, to prevent recurrence and the treatment if such occurs, based on the pathogenesis of HCC.
Carcinoma, Hepatocellular↗
[Second resected hepatocellular carcinoma of multicentric occurrence suspected by clinical follow-up].
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Aged↗
Studies on the relationship between hepatic and splenic density change in dynamic CT in the presence of a large splenorenal shunt in patients with liver cirrhosis.
Using dynamic computerized tomography (CT), we studied liver and spleen hemodynamics in one group of patients with a large splenorenal shunt and another group without a large shunt. Specifically, we measured the time-to-peak hepatic and splenic enhancement and the loss of enhancement, i.e., decay time. The time-to-peak liver enhancement (61 +/- 21 s vs. 81 +/- 14 s, p < 0.05) and the splenic decay time (24 +/- 16 s vs. 48 +/- 28 s, p < 0.05) were significantly shorter in patients with a large splenorenal shunt compared to those without. The groups had similar hepatic decay times and times to peak splenic enhancement. We found dynamic CT useful in assessing the effect of a large splenorenal shunt on portal and splenic hemodynamics.
Adult↗
Bilateral lobectomy excluding the caudate lobe for giant mesenchymal hamartoma of the liver.
A girl underwent partial resection of the liver for mesenchymal hamartoma twice, at 7 months and again at 3 years of age. When the patient was 16 years of age, the mass increased rapidly in size. The patient was hospitalized and studied by ultrasonography, computed tomographic scans, and arterial angiography. The tumor occupied the right and left lobes of the liver, but the hypertrophic caudate lobe in which no tumor was found could provide satisfactory liver function, so the tumor was extirpated by bilateral lobectomy, with preservation of the caudate lobe. Histologic examination of the operative specimen led to the diagnosis of typical mesenchymal hamartoma of the liver. Malignancy was not found. About 30 cases of this disorder have been reported in Japan, and about 100 cases have appeared in the literature in English. To the best of our knowledge, no earlier reports of bilateral lobectomy have been made.
Adolescent↗
Antidepressive effects of the stereoisomer cis-dosulepin hydrochloride.
The central action of cis-dosulepin (CAS 113-53-1) was compared with that of its antidepressant stereoisomer trans-dosulepin, cis-dosulepin exerted weaker anti-reserpine, anti-tetrabenazine, and 3H-5-HT (serotonin) uptake inhibiting actions than trans-dosulepin, but cis-dosulepin's inhibition of 3H-dopamine and 3H-norepinephrine uptake was slightly more potent than that of trans-dosulepin. On the other hand, cis-dosulepin exhibited extremely potent anticholinergic action in oxotremorine induced tremor, isolated ileums and the 3H-quinuclidinyl benzilate binding test. It also showed potent apomorphine enhancing action and shortened the period of immobility in the forced swimming test in animals. The pharmacological profile of cis-dosulepin appears interesting with respect to investigating the mechanism of action of antidepressants.
Acetylcholine↗
The strain-dependent constitutive expression of murine serum amyloid-P component is regulated at the transcriptional level.
The strain-dependent expression of murine serum amyloid P-component (SAP) has been known to be linked to the Sap locus. We have quantified the SAP mRNA in several inbred strains including DBA/2 and C57BL/6 mice which represent high and low producers of SAP at resting state, respectively, and found that the mRNA levels correlated well with the amount of SAP protein. Interestingly, the SAP mRNA level of F1 mouse between DBA/2 and C57BL/6 was low and similar to that of C57BL/6. Primer extension and ribonuclease (RNAase) protection analyses demonstrated that a single type of transcript was generated from the SAP gene and that the cap sites were identical regardless mouse strains tested under unstimulated and stimulated (by lipopolysaccharide (LPS) or interleukin-6 (IL-6)) conditions. To investigate possible structural difference of the SAP gene including 5' flanking region, we have cloned, sequenced and compared the SAP genes from DBA/2 and C57BL/6 mice. Sequence analyses revealed that the 5' flanking regulatory regions, as well as the coding regions, were well-conserved between the two strains. These results demonstrate that the strain-dependent SAP expression occurs at the transcriptional level but seems to be affected by neither different type of the transcripts nor structural difference of the 5' flanking and coding regions of the SAP gene. It was suggested that a possible transcription factor with suppressive activity, which is encoded by a gene linked to Sap, may be involved.
Animals↗
Measurements of CSF biochemical tumor markers in patients with meningeal carcinomatosis and brain tumors.
CSF beta-glucuronidase, polyamines and carcinoembryonic antigen (CEA) were analyzed in 16 patients with meningeal carcinomatosis from solid tumor in systemic organs, 27 with benign brain lesions, 18 with primary brain tumors, 14 with metastatic brain tumors and 5 with leptomeningeal dissemination of other malignant diseases. Beta-glucuronidase levels in all cases of meningeal carcinomatosis, meningeal gliomatosis and meningeal lymphoma were higher than 100 micrograms/dl/hr; on the other hand, levels in all cases of benign brain lesions were below 100 micrograms/dl/hr. Levels of beta-glucuronidase and polyamines were not high in the cases with positive cytology after tumor resection. Polyamine levels were below 0.05 nmol/ml in all cases after resection of the metastatic brain tumor. Cystic fluid of malignant tumors showed high levels of beta-glucuronidase and polyamines. On the other hand, the levels of polyamines in the cystic fluid of benign tumor were low, although the levels of beta-glucuronidase were high. Some cases of meningeal carcinomatosis with high levels of serum CEA did not show high levels of CSF CEA. For metastatic brain tumors, the cases with intraparenchymal tumors, especially with dural attachment showed high levels of beta-glucuronidase and CEA preoperatively, but they returned to normal after surgery. In cases of meningeal carcinomatosis treated by intrathecal chemotherapy with methotrexate (MTX) and cytosine arabinoside (Ara-C), CSF beta-glucuronidase reflected the neurological status better than the cell count decreased rapidly following chemotherapy and beta-glucuronidase was considered as a useful CSF marker in cases of meningeal carcinomatosis to monitor the course of the disease. The same situation was observed in CSF CEA and CEA was also considered as a useful marker when CEA levels in CSF are higher than those in serum.
Antineoplastic Agents↗
Diagnosis and treatment of patients with meningeal carcinomatosis.
The records of thirty-four patients with meningeal carcinomatosis treated at our hospital between 1984 and 1990 were reviewed. The sources, histologies, metastatic lesions outside the central nervous system, the history of the treatment of primary lesions and intraparenchymal of metastatic brain tumors and the period from the diagnosis of primary lesions and the treatment of intraparenchymal metastatic brain tumors to the diagnosis of meningeal carcinomatosis were investigated. Meningeal carcinomatosis was diagnosed and by neurological signs, CSF cytology, CT scan and MRI. Each patient was given a 5 mg single dose of methotrexate (MTX) alone or combined with 20 mg cytosine arabinoside (Ara-C) administered by intrathecal injection via an Ommaya reservoir and standard lumbar puncture with or without radiotherapy. Following intrathecal chemotherapy 22 of 29 patients showed symptomatic improvement of meningeal irritation and in 10 of 29 patients with cranial nerve impairment amelioration of symptoms was also observed. Moreover, CSF cytology became negative in 10 of 29 patients after a full course of intrathecal chemotherapy. Neurotoxicity Leukoencephalopathy, a neurotoxic effect of intrathecal chemotherapy was not observed in any of the patients. From these results, MTX in small doses is recommended for intrathecal chemotherapy of meningeal carcinomatosis to prevent neurotoxicity.
Antineoplastic Combined Chemotherapy Protocols↗
Participation of poly(ADP-ribose) polymerase in the drug sensitivity in human lung cancer cell lines.
Poly(ADP-ribose) polymerase has been generally assumed to be involved in DNA repair. The level of the enzyme in various lung cancer cell lines was examined to determine if it is involved in drug resistance. Among nine cell lines of lung cancer tested, small-cell lung cancer lines, which showed higher sensitivity to cisplatin and etoposide, were unexpectedly found to contain significantly higher poly(ADP-ribose) polymerase activity than five non-small-cell lung cancer cell lines. This activity inversely correlated with IC50 values of lung cancer cell lines to etoposide, an inhibitor of topoisomerase II. The polymerase activity was also examined in several cisplatin-resistant variants of the cell lines. However, no difference was observed between parental and cisplatin-resistant cells. There was no significant relation between poly(ADP-ribose) polymerase activity and IC50 values for cisplatin and carboplatin. Although this enzyme was considered to play some role in the resistance to specific drugs, it might not be a critical factor in cisplatin-induced cytotoxicity.
Antineoplastic Agents↗