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T Meguro

Publications and source records attributed to T Meguro.

At least 73 records · Page 4Linked to original sources

Extracellular Nef protein regulates productive HIV-1 infection from latency.

In HIV-1-infected asymptomatic carriers, the vast majority of infected cells in PBMCs are believed to be latently or nonproductively infected. We have isolated a subclone (MOLT-20-2) from an infected T cell line that expressed HIV-1 Ags at a very low level. However, viral Ag expression was markedly up-regulated by stimulation with either TNF-alpha, A23187, or PMA, indicating that the subclone might provide a suitable model of HIV-1 latency. Our previous studies have shown that the carboxyl-terminal region of the extracellular form of HIV-1 Nef played an important role in the interaction of infected cells with uninfected T cells, and could induce the cytostatic state. This suggested that Nef might contribute to intracellular signal transduction through an interaction with latently infected cells. We show in this study that stimulation of MOLT-20-2 with soluble Nef leads to HIV-1 activation from latency in a dose-dependent manner. Moreover, using a total of 14 overlapping Nef-related synthetic peptides, stimulatory activity was mapped to a discrete peptide (amino acid residues 132-147) that had the potential to activate latent HIV-1. This novel Nef function was confirmed by activation of virus production from the PBMCs of asymptomatic carriers. In addition, Nef-dependent HIV-1 activation from latency was also observed in another independently derived, latently infected cell line, U1, though not in cell line ACH-2. These results extend the significance of the Nef activity in vivo to the regulation of productive HIV-1 infection from latency, and define the regions of the protein involved.

Amino Acid Sequence↗

Effects of cisapride on gallbladder emptying and pancreatic polypeptide and cholecystokinin release in humans.

We investigated the effects of cisapride on gallbladder motility and on the release of pancreatic polypeptide and cholecystokinin in the fasting and postprandial states. Cisapride (7.5 mg) and/or a test meal was administered intraduodenally to seven healthy volunteers with or without atropine pretreatment (0.5 mg, i.m.). In the fasting state, cisapride increased gallbladder volume to 154% of the basal level, and significantly elevated plasma pancreatic polypeptide levels. The effects of cisapride were inhibited by atropine. In the postprandial state, integrated pancreatic polypeptide and cholecystokinin responses were increased by cisapride to 180% and 192%, respectively, of control values. Atropine inhibited the integrated gallbladder and pancreatic polypeptide response to about 60% of the control value, but did not affect the cholecystokinin response. These observations suggest that: (1) fasting gallbladder tone is influenced by cholinergic inhibitory mechanisms, (2) acetylcholine (ACh) is the final mediator for about 40% of the postprandial gallbladder emptying and pancreatic polypeptide response, and (3) coordination between the ACh-independent cholecystokinin response and ACh-dependent pancreatic polypeptide response may be important in the regulation of postprandial gallbladder emptying.

Adult↗

Progress in the management of patients with aneurysmal subarachnoid hemorrhage: a single hospital review for 20 years. Part I: Younger patients.

BACKGROUND: This study was carried out to clarify if there has been any improvement in the outcome of patients with aneurysmal subarachnoid hemorrhage during the past 20 years. Because elderly patients have apparently poorer prognoses than younger patients, patients older than 70 years were analyzed separately in the following article. METHODS: Five hundred seventy-one patients with aneurysmal subarachnoid hemorrhage, under 70 years, who were consecutively admitted to Kagawa Prefectural Central Hospital from July 1972 to December 1992, were reviewed. These patients were divided into four groups according to the time of admission. The ultimate outcome was evaluated by means of Glasgow Outcome Scale 6 months after the ictus. RESULTS: Changes in treatment protocol in this period included the induction of early surgery and the invention of a variety of modalities for the treatment of cerebral vasospasm. This resulted in a distinct increase in patients who actually underwent direct aneurysm clipping. Outcome has been significantly improved during this period, especially in patients with Hunt and Kosnik grade III (p<0.05, chi2). Patients in good clinical condition at follow-up (Glasgow Outcome Scale: good recovery) increased from 8.7% to 60.7%. Mortality decreased from 28.7% to 10.7%. CONCLUSIONS: Current therapeutic modalities have significantly improved the outcome of patients with aneurysmal subarachnoid hemorrhage. Rebleeding before early surgery remains as a major cause of unfavorable outcome and further progress on this subject is mandatory.

Aged↗

Progress in the management of patients with aneurysmal subarachnoid hemorrhage: a single hospital review for 20 years. Part II: Aged patients.

BACKGROUND: We have reported improvement in the outcome of the younger patients with aneurysmal subarachnoid hemorrhage in the preceding article. The purpose of this article is to study if the same management protocol has simultaneously benefited the elderly patients. METHODS: One hundred twenty-nine patients with aneurysmal subarachnoid hemorrhage, over 70 years old, who were consecutively admitted to Kagawa Prefectural Central Hospital from July 1972 to December 1992, were reviewed. Patient grouping and outcome evaluation were the same as those of younger patients. RESULTS: Changes in treatment protocol in this period, which were similar to those of the younger counterparts, resulted in an increased number of patients who actually underwent aneurysm clipping. Although the outcome evaluated at 6 months after initial hemorrhage was significantly poorer than that of the younger counterparts, there have been some improvements during the study period. Patients in good clinical condition at 6 months' follow-up (Glasgow Outcome Scale: Good Recovery) increased from 37.5% to 42.9% in grades I-II and from 0% to 23.1% in grade III, respectively. CONCLUSIONS: The improvement in the outcome of elderly patients was less remarkable than that observed in younger patients. Significantly higher incidence of preoperative rebleeding and postoperative symptomatic vasospasm has proven to be the major cause of mortality and major morbidity at present. More careful and sophisticated perioperative care is required in elderly patients with aneurysmal subarachnoid hemorrhage.

Aged↗

Combined cisternal drainage and intrathecal urokinase injection therapy for prevention of vasospasm in patients with aneurysmal subarachnoid hemorrhage.

The effect of cisternal drainage and intrathecal urokinase injection in preventing symptomatic vasospasm (SVS) after aneurysmal subarachnoid hemorrhage was studied in 60 patients with uniform background (Hunt & Kosnik grade III, younger than 70 yrs, undergoing surgery within 72 hrs after hemorrhage). The incidence of permanent neurological deficits caused by vasospasm was 5/16 without cisternal drainage, 5/34 with drainage alone, and 1/10 with drainage and urokinase injection. Analysis of patients without postoperative cisternal drainage showed the amount of subarachnoid clot on the initial computed tomographic scan was closely related to the occurrence of SVS (p < 0.05, unpaired t test). Analysis of patients with cisternal drainage showed the amount of bloody cerebrospinal fluid (CSF) drained during the 10 days after surgery and the duration of drainage placement were critical in preventing vasospasm (p < 0.05, unpaired t test). Greater CSF drainage significantly reduced the incidence of permanent neurological deficits caused by vasospasm (p < 0.01, chi 2), but significantly increased the incidence of hydrocephalus requiring shunt procedures (p < 0.01, chi 2). Urokinase injection via cisternal drainage achieved a further reduction in the occurrence of SVS. Intrathecal thrombolytic therapy after aneurysmal surgery is an effective method for SVS prophylaxis, and CSF drainage (> 1500 ml for 10 days) enhances the effect.

Brain↗

Life time expectancy of hemophilia patients infected with HIV-1 with the risk of hepatocellular carcinoma after HCV infection.

1. INTRODUCTION. The latest statistics how that Japanese hemophilia patients infected with HIV-through clotting factor concentrates may survive more than 10 years after HIV-infection without showing an onset of AIDS [1]. Unfortunately, however, results of the recent surveillance have revealed that about half of hemophilia patients had also been infected with the hepatitis C virus (HCV) [2]. Therefore, some hemophilia patients might suffer from hepatocellular carcinoma triggered by HCV after some latent periods. In the present study, we computed the life time expectancy of hemophilia patients with two risks of HIV-and HCV infections. 2. METHOD. We used the Weibull hazard function h(t) for the hazard rate from AIDS after infection with HIV-1. In order to describe the hazard rate arising from hepatocellular carcinoma after HCV infection, we utilized the theoretical function c(t) with two parameters that were obtained previously by ourselves from a case-controlled study on hepatocellular carcinoma patients infected with HCV through blood transfusion [3]. Substituting necessary parameters estimated for Japanese hemophilia patients into h(t), the life time expectancy t was computed by the following integration; tau=integral of exp(-integral of h(t')+c(t¿) dt') dt, where t' means the time after HIV-infection, and t¿ is a variable composed of tU and times of HIV-and HCV infections. 3. RESULTS AND DISCUSSION. Without hepatocellular carcinoma, the life time expectancy tau of the patients infected with HIV-1 at the age of 20 was computed as 15.0 years. On the other hand, for the same patients with the risk of hepatocellular carcinoma through HCV infection at the age of 10, 15, 20 and 25 years old, values of tau were computed at 12.2, 13.3, 14.1 and 14.4 years, respectively. Especially noticeable was the reduction of tau in cases of HCV infection was prior to HIV-infection. In the present computation, the two risks from HIV-1 and HCV infections were assumed to be additive because no explicit interaction between them has been reported yet. Various long term effects have been found with the development of HIV/HCV therapies; that should also take into account the survival estimation and therapy planning for HIV-1 infected patients in the coming years.

Acquired Immunodeficiency Syndrome↗

Role of Helicobacter pylori in chronic gastritis: a prospective study.

We conducted a prospective study to evaluate the relationship between Helicobacter pylori infection and chronic gastritis in a Japanese population. H. pylori was found in 67% of patients positive for mononuclear cell (MN cell) infiltration and in 75.8% of patients positive for polymorphonuclear cell (PMN cell) infiltration, whereas H. pylori was found in 14.2% of patients without MN cell infiltration and in 33.2% of patients without PMN cell infiltration. The frequency of MN and PMN cell infiltration in H. pylori-positive patients was significantly higher than that in H. pylori-negative patients. The frequency of H. pylori infection did not differ in those with atrophic gastritis from those without, whereas the frequency of intestinal metaplasia became significantly higher in those with moderate and severe atrophy. There was no significant difference between serum pepsinogen I (PG I) levels in H. pylori-positive and -negative patients. However serum PG II levels were significantly increased in H. pylori-positive patients aged 40-69 years. The serum PG I-II ratio was significantly lower in H. pylori-positive patients aged 40-59 years. These results suggest that H. pylori infection in the gastric mucosa plays an important role in the pathogenesis of chronic and atrophic gastritis and in the development of intestinal metaplasia.

Adult↗

Effect on short-term prognosis and left ventricular function of angina pectoris prior to first Q-wave anterior wall acute myocardial infarction.

The prognostic significance of angina pectoris before the development of first Q-wave anterior wall acute myocardial infarction (AMI) was assessed in 153 patients. A total of 100 patients in this study had angina before Q-wave AMI, whereas 53 patients had no antecedent symptoms of angina. The presence of angina before AMI was associated with a lower incidence of complications including sustained ventricular tachycardia or fibrillation (7% vs 25%, p = 0.0022), pump failure (24% vs 47%, p = 0.0035), cardiac rupture (1% vs 17%, p = 0.0001), and a lower in-hospital mortality rate (11% vs 28%, p = 0.0067). The peak creatine phosphokinase activity was lower in patients with than without antecedent angina (1,727 +/- 1,238 vs 2,675 +/- 2,569 IU/liter, respectively, p = 0.023). There was no difference in the prevalence of multivessel coronary artery disease or the presence of collateral circulation between the 2 groups. Left ventriculography revealed a higher left ventricular ejection fraction (54 +/- 13% vs 46 +/- 11%, p = 0.034) and smaller left ventricular end-diastolic volumes (75 +/- 15 vs 86 +/- 18 ml/m2, p = 0.017) in patients with than without antecedent angina. These findings suggest that the presence of angina before AMI may be associated with a protective effect on left ventricular function during anterior wall AMI. Although the precise mechanisms underlying the beneficial effects are unknown, they may be related to the development of collateral channels or ischemic preconditioning.

Adult↗

Alteration of aldolase isozymes in serum and tissues of patients with cancer and other diseases.

We studied the alteration of aldolase isozymes in the serum and tissues of patients with cancer and other diseases using radioimmunoassays specific for aldolase A, B, and C subunits. Aldolase B was predominantly found in adult liver, where aldolase A and C were distinctly low. Aldolase A and B showed almost the same concentration in fetal liver, while in neonatal liver aldolase B protein concentrations were much higher than aldolase A. In contrast, aldolase A was the predominant isozyme found in hepatoma and gastric cancer tissues, whereas aldolase B was distinctly low in hepatoma tissues, and extremely low in gastric cancer tissues. These results suggest that the aldolase A is a more fetal type of liver isozyme than the aldolase B and C, and aldolase B is a more differentiated type of liver isozyme than aldolase A and C. Serum FDP aldolase activities were elevated in half of patients with liver diseases, all patients with muscle diseases and a few patients with cancer. Serum aldolase A levels were elevated in patients with muscle diseases and cancer, but not elevated in patients with liver diseases. In contrast, serum aldolase B levels were elevated in patients with liver disease, but not elevated in patients with muscle diseases and other diseases without liver injury. Serum aldolase B levels showed a trend to decrease in cancer patients with normal GPT levels. Serum aldolase A/B ratios were significantly increased in cancer patients with normal GPT levels, whereas they showed the decreased levels in patients with liver diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Fructose-Bisphosphate Aldolase↗

Hepatitis C virus antibodies, viral RNA and genotypes in sera from patients on maintenance haemodialysis.

Patients on maintenance haemodialysis in four dialysis centres were tested for markers of hepatitis C virus (HCV) infection. Antibody to HCV (anti-HCV) was detected by the second-generation enzyme immunoassay in 142 (26%) of the 543 patients and HCV RNA in 117 (22%) of whom four were without detectable anti-HCV in serum. Seventy-seven (66%) were infected with HCV of genotype II/1b, 31 (27%) with genotype III/2a and eight (7%) with genotype IV/2b, in a distribution similar to that in blood donors who carried HCV asymptomatically. Haemodialysis patients had high HCV RNA titres comparable to those of patients with chronic hepatitis C. HCV RNA was detected in 96 (26%) of the 365 patients with a history of transfusion more frequently than in 21 (12%) of the 178 without previous transfusion (P < 0.001). In transfused patients, frequencies of anti-HCV and HCV RNA increased in parallel with the duration of haemodialysis. The frequency of anti-HCV in non-transfused patients, however, did not change appreciably with the duration of haemodialysis up to 22 years. The patients with anti-HCV had a higher frequency of HCV RNA in serum than symptom-free blood donors with anti-HCV (113/142 or 80% vs 109/166 or 66%, P < 0.01) and the patients with HCV RNA had a lower frequency of elevated aminotransferase levels than blood donors with HCV RNA (5/113 or 4% vs 27/109 or 25%, P < 0.001). These results indicate that transfusion is a significant cause of HCV infection in patients on maintenance haemodialysis, and that these patients are prone to establish the HCV carrier state after infection.

Adult↗

The role of Helicobacter pylori infection in the pathogenesis of gastritis.

We conducted a prospective study to evaluate the relationship between H. pylori infection and gastritis in a Japanese population. The study population consisted of 92 patients with endoscopically proven gastritis. Biopsy specimens were taken from the gastric mucosa from the corpus and antrum according to the Sydney system for the new classification of gastritis. H. pylori was histologically found in 84.3% of patients for mononuclear (MN) cell infiltration and in 88.1% of those positive for polymorphonuclear (PMN) cells. H. pylori was not found in any of nine patients without MN cell infiltration (P < 0.001), while 68.8% of patients without PMN cell infiltration were positive for H. pylori (P < 0.03). The frequency of MN cell infiltration in H. pylori-positive patients was significantly higher than that in H. pylori-negative patients (100% vs 65.4%; P < 0.001). The frequency of PMN cell infiltration in H. pylori-positive patients was also significantly higher than that in H. pylori-negative patients (54.5% vs 23.1%; P < 0.01). The incidence of MN cell infiltration in the antrum was significantly higher than that in the gastric corpus in H. pylori-positive gastritis patients (93.2% vs 65.1%; P < 0.001). The incidence of PMN cell infiltration was also higher in the antrum than in the corpus in H. pylori-positive gastritis patients, although the difference was not significant (42.0% vs 31.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Gastric Mucosa↗

Causal role of Helicobacter pylori in peptic ulcer relapse.

Helicobacter pylori has been shown to infect the gastric mucous layer of almost all patients with duodenal ulcer disease, as well as that of most patients with gastric ulcer disease. Recent studies have suggested that the eradication of H. pylori affects the natural history of duodenal ulcer disease such that the rate of relapse decreases markedly. We evaluated the relationship between H. pylori infection and peptic ulcer relapse in a Japanese population following a prospective study. Seven of 18 (38.9%) gastric ulcer patients positive for H. pylori relapsed by the end of 1 year, whereas only 1 of 9 (11.1%) gastric ulcer patients without H. pylori developed ulcer relapse (P < 0.05). Relapse rates of duodenal ulcer patients negative for H. pylori were significantly lower than those positive for H. pylori within 1 year (0% vs 66.7%; P < 0.01). The effects of anti-H. pylori drugs on the eradication of H. pylori were examined in 50 patients with peptic ulcers. Eradication rates with a proton pump inhibitor (PPI) alone (omeprazole 20 mg) showed the lowest values (4 of 13; 30.8%). The rates were: 44.4% for amoxicillin alone (4 of 9); 70% for triple therapy consisting of amoxicillin, metronidazole, and bismuth subnitrate (14 of 20); and 87.5% for concomitant therapy of the PPI plus amoxicillin (7 of 8). Reinfection rates of H. pylori within 1 year after eradication of this organism were distinctly higher in the PPI alone group (80%) than in other groups (18.2%-32.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Measurement of fecal hemoglobin-haptoglobin complex as a new diagnostic tool of lower gastrointestinal tract diseases].

An immunoradiometric assay (IRMA) of human hemoglobin-haptoglobin complex (Hb-Hp complex) was established for the purpose of clinical application as a new fecal occult blood test. This IRMA reacted with free human Hb and Hp as well as Hb-Hp complex and its measurable range was 3.125 through 800 ng/ml. Its cross-reaction with other animal Hb and serum was little enough to neglect. The immunoreactivity of Hb-Hp complex was more stable than that of free Hb in incubation with gastric juice and fecal extracts. Of 48 stools from the patients with colorectal cancer, 44 (91.7%) gave positive (above 10 ng/ml in fecal extract) test in Hb-Hp complex-IRMA, whereas 35 (72.9%) (p < 0.05) gave positive result (above 10 ng/ml in fecal extract) in Hb-IRMA. At proximal site of cancer, positive rate of Hb-Hp complex in feces was significantly high (p < 0.05) compared with Hb. Of 64 stools from the patients with colorectal adenomas, 56 (87.5%) gave positive test in Hb-Hp complex, whereas 46 (71.9%) (p < 0.05), 28 (43.8%) (p < 0.01) and 33 (51.5%) showed positive in Hp, Hb and Guaiac test, respectively. In every size and site of adenoma, fecal Hb-Hp complex showed significantly high (p < 0.01) positivity compared with Hb and Guaiac test. These results suggest that the measurement of Hb-Hp complex in fecal extracts may be a useful tool for the early detection of lower gastrointestinal diseases.

Animals↗

Gallbladder emptying to endogenous and exogenous stimulation in chronic pancreatitis patients.

OBJECTIVES: The present study was designed to analyze the underlying mechanism of gallbladder motor disturbance in chronic pancreatitis patients. METHODS: Gallbladder emptying to endogenous (oral test meal, Daiyan 13 g) and exogenous stimulation (iv cerulein, 30 ng/kg for 5 min) was examined by real-time ultrasonography in 12 patients with chronic pancreatitis and 10 normal subjects (controls). Plasma cholecystokinin levels during the endogenous stimulation were measured by bioassay. RESULTS: In chronic pancreatitis patients compared with controls, the fasting gallbladder volume was significantly increased (29.5 +/- 2.2 vs. 21.5 +/- 2.8 ml), whereas the gallbladder emptying (percent change of the basal volume) to oral test meal was significantly decreased. Neither cholecystokinin secretion induced by the test meal, nor the gallbladder emptying response to intravenous cerulein, differed significantly between the two groups. However, when chronic pancreatitis patients were divided according to pathogenesis, it became clear that gallbladder emptying to intravenous cerulein was significantly greater in patients with alcoholic chronic pancreatitis than in patients with idiopathic pancreatitis. CONCLUSIONS: Gallbladder emptying during the intestinal phase is generally reduced in patients with chronic pancreatitis, but gallbladder responsiveness to exogenous stimulation might be heterogeneous according to the pathogenesis.

Adult↗

The role of Helicobacter pylori in peptic ulcer disease.

The linking of relapse of duodenal as well as gastric ulcers with Helicobacter pylori (H. pylori) has been a considerable advance in managing patients with peptic ulcer disease. However, pathogenetic role of H. pylori in peptic ulcer still remains unclear. The aim of this study was to assess the relationship between H. pylori infection and inflammatory cell infiltration in gastric mucosa in peptic ulcer disease. Sixty-four patients with endoscopically proven gastric ulcer and 26 patients with duodenal ulcer were evaluated by prospective study. Biopsy specimens were taken from the ulcer margin, corpus and antrum. Eradication of H. pylori was attempted by concomitant administration of amoxycillin 500 mg, metronidazole 250 mg and bismuth subnitrate 1 g twice daily for 2 weeks. H. pylori positive rates in clinical stages of gastric and duodenal ulcer showed almost the same values of more than 90%. The prevalence of H. pylori at the antrum and corpus was almost the same as that between gastric and duodenal ulcer patients, whereas a dramatic difference in the positive rates at the ulcer margin was observed between gastric and duodenal ulcer patients (83.9% and 35.0%, respectively). The prevalence of polymorphonuclear (PMN) cell infiltration at the ulcer margin was still high even at the scarring stage of gastric and duodenal ulcer with positive H. pylori, whereas a dramatic decrease of PMN cell infiltration was observed at the ulcer margin after successful eradication of H. pylori. These results suggest that H. pylori may play an important role in the pathogenesis of gastric and duodenal ulcer by inducing inflammatory cells such as PMN cells in gastric mocosa.

Amoxicillin↗

Differentiation of transiently ischemic from infarcted myocardium by thallium-201 exercises scintigram after active ergometer rehabilitation.

It has been frequently reported that while myocardial viability is neglected in conventional methods of diagnosis such as left ventriculography, ECG, and exercise thallium-201 myocardial scintigraphy (Ex-Tl), revascularization often results in improving left ventricular wall motility. In the present study, the authors contrived a method to accurately evaluate the viability of the myocardium by means of exercise rehabilitation, and tested the method in clinical cases. Among patients with myocardial infarction, we selected a patient with negative viability in the diseased area as determined by chronic ECG, left ventriculography (LVG), coronary angiography and Ex-Tl. This patient went through two weeks of active exercise rehabilitation gauged with an ergometer, and was then re-examined by Ex-Tl. After the evaluation, revascularization was performed for the patient who demonstrated viability of the infarcted myocardium in EX-Tl after rehabilitation, and significant improvement in contractility was shown in the chronic LVG. These findings indicate that our method of detecting potential viability of the infarcted myocardium is of clinical significance.

Ergometry↗

Neurons containing gastrin releasing peptide-like immunoreactivity in the human pancreas.

Gastrin releasing peptide (GRP) is known to stimulate pancreatic enzyme and islet hormone secretion. In the present immunohistochemical study, the localization and distribution of GRP-like immunoreactivity were investigated in the human pancreas using two antisera with different specificities. GRP-like immunoreactivity (GRP-LI) was observed in numerous nerve fibers diffusely distributed to the exocrine pancreas, but was not seen in intrapancreatic nerve cells of normal pancreatic specimens examined. Nerve fibers and terminals with GRP-LI were found in abundance around pancreatic acini and capillaries, with moderate density around ductules and in the walls of arterioles, and a few were seen in islets. This distribution pattern was quite similar to that of vasoactive intestinal polypeptide (VIP)-LI nerve fibers. The study, using the antibody elution method, strongly suggests the co-localization of GRP- and VIP-LIs within a part of VIP-containing nerve fibers. In the chronic pancreatitis specimens, neurons with GRP-LI were frequently found, and > 90% of intrapancreatic nerve cells were VIP-immunoreactive. Immunostainings for GRP and for VIP on serial adjacent sections of intrapancreatic ganglia from chronic pancreatitis specimens suggested the co-localization of the two immunoreactivities in > 70% of intrapancreatic neurons. The present findings may provide a morphological basis for neurotransmitter and/or neuromodulator roles of GRP in the human pancreas.

Antibody Specificity↗

Hypofibrinogenemia in a girl with Langerhans cell histiocytosis during etoposide and prednisolone therapy.

A case of a girl with Langerhans cell histiocytosis who had hypofibrinogenemia during etoposide (VP-16) and prednisolone therapy is described. A patient on a three times per week schedule of 100 mg/m2 etoposide in combination with 40 mg/m2 of prednisolone every day had hypofibrinogenemia of 90 mg/dL after 12 doses of etoposide. Hypofibrinogenemia improved after discontinuing the course of etoposide. The clinical course suggested that the combination of etoposide with prednisolone caused this side-effect. Although the exact mechanism of toxicity of etoposide with prednisolone remains unknown, it is possible that the side-effect might be due to reduced production of fibrinogen in the liver. Careful monitoring of fibrinogen is mandatory in patients receiving etoposide and prednisolone.

Afibrinogenemia↗