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Biomedical subjects

M Jaakkola

Publications and source records attributed to M Jaakkola.

At least 19 recordsLinked to original sources
PubMed1997

Structures of the human gene for the protein disulfide isomerase-related polypeptide ERp60 and a processed gene and assignment of these genes to 15q15 and 1q21.

ERp60 (also known as ERp61 or GRP58) is an isoform of protein disulfide isomerase (PDI) that has two thioredoxin-like domains a and a' in positions corresponding to those of domains a and a' in the PDI polypeptide and shows a significant amino acid sequence similarity to PDI in almost all parts. We report here that the human ERp60 gene is about 18 kb in size and consists of 13 exons. No distinct correlation was found between its exon-intron organization and the modular structure of the ERp60 polypeptide, nor were any similarities in exon-intron organization found between the human ERp60, PDI, and thioredoxin genes. The 5' flanking region of the ERp60 gene has no TATAA box or CCAAT motif but contains several potential binding sites for transcription factors. The highest levels of expression of the ERp60 mRNA were found by Northern blotting in the liver, placenta, lung, pancreas, and kidney, and the lowest in the heart, skeletal muscle, and brain. We also isolated an intronless ERp60 gene that probably represents a pseudogene. The ERp60 gene was mapped by fluorescence in situ hybridization to 15q15 and the processed gene to 1q21, so that neither was located on the same chromosome as the human PDI and thioredoxin genes.

Amino Acid Sequence↗
PubMed1997

The presence of the gallbladder is associated with the severity of acute biliary pancreatitis.

CONCLUSION: The presence of the gallbladder at the onset of acute biliary pancreatitis is associated with increased severity of the disease. One possible explanation is that gallbladder contraction might induce bile reflux into the pancreatic duct during the transfer of a gallstone through the ampulla. BACKGROUND: In clinical practice there is an impression that the presence of the gallbladder in patients with biliary pancreatitis may be associated with increased severity of the disease, compared to patients who have undergone cholecystectomy. METHODS: To test this hypothesis, we studied 266 cases with biliary pancreatitis. Patients were divided into two groups: (A) those who had a gallbladder in situ at the onset of biliary pancreatitis (n = 234, 88%) and (B) those who had undergone previous cholecystectomy (n = 32, 12%). RESULTS: Pancreatitis was more severe in group A than in group B, according to Glasgow criteria (> or = 3 positive, 66/210 = 31% vs 4/29 = 14%, p = 0.04); development of complications (77/234 = 33% vs 4/32 = 13%, p = 0.01); and mortality (40/234 = 17% vs 1/32 = 3%, p = 0.03). Furthermore, serum C-reactive protein levels on admission were over 150 mg/L twice as often in group A as in group B.

Acute Disease↗
PubMed1996

In vitro concurrent paclitaxel and radiation of four vulvar squamous cell carcinoma cell lines.

BACKGROUND: The antitubule agent paclitaxel causes a cell cycle blockage in the most radiosensitive part of the cell cycle, the G2/M phase. The possible radiosensitizing effect of paclitaxel was tested in four vulvar (UM-SCV-1A, UM-SCV-1B, UM-SCV-2, and UM-SCV-4) squamous cell carcinoma (SCC) cell lines. METHODS: A 96-well plate clonogenic assay was performed with paclitaxel and radiation, both separately and concomitantly. Survival data were fitted to the linear quadratic model. The area under the curve, equivalent to the mean inactivation dose (D), was obtained by numerical integration. The effect of paclitaxel on radiosensitivity was measured as the AUC ratio (paclitaxel plus radiation: radiation alone). This ratio was compared with the surviving fraction (SFP) after paclitaxel alone. RESULTS: Paclitaxel concentrations of 0.4 to 2.0 nanomolar (nM) caused 1 to 70% inhibition of clonogenic survival. The AUC values of the cell lines were 1.9 to 2.9 gray. A full additive effect was observed when paclitaxel and radiation were administered concurrently; however, a supra-additive effect never occurred. The type of paclitaxel radiation interaction was not affected by the concentration of the drug nor did the type of interaction vary between cell lines studied. CONCLUSIONS: Paclitaxel and radiation used concomitantly produced a clear additive effect at all concentrations and in all vulvar carcinoma cell lines tested. Although no supra-additive effect was observed, the additive effect already in nM concentrations could be beneficial in clinical use and, therefore, requires further investigation.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Acute pancreatitis in patients over 80 years.

OBJECTIVE: To evaluate the occurrence, aetiology and outcome of acute pancreatitis (AP) in patients over 80 years of age, compared with those between 61 and 79 years old. DESIGN: Retrospective analysis. SETTING: University hospital, Finland. SUBJECTS: Subgroups of 22 patients 80 years old or over and 139 patients 61-79 years old out of 1058 episodes of AP between 1982 and 1990. MAIN OUTCOME MEASURES: Mortality, morbidity, and hospital stay. RESULTS: The percentage of patients aged 80 or more varied from 0 in 1982 to 3% in 1990; 13 (59%) were women compared with 47 (34%) in the 61-79 year old group (p = 0.03). AP in the older group was more likely to be necrotising 9/22 (41%) compared with 23/139 (17%), p = 0.02) and to have been caused by biliary disease 15/22 (68%) compared with 54/139 (39%), (p = 0.01). The overall mortality was 9/22 (41%) in the 80 years and over group and 24/139 (17%) in patients aged 61-79 years (p = 0.02). All 9 patients in their eighties with necrotising pancreatitis died. Neither the mode of treatment nor the Glasgow prognostic scoring had any relation to mortality in the older group. CONCLUSIONS: AP in patients of 80 or more is a serious disease with a high mortality irrespective of standard treatment.

Acute Disease↗
PubMed1995

Serum tumour necrosis factor compared with C-reactive protein in the early assessment of severity of acute pancreatitis.

Tumour necrosis factor (TNF) is an early mediator of sepsis and multiple organ failure; increased concentrations in serum are also observed in acute pancreatitis. In the present study the predictive value of TNF and C-reactive protein (CRP) concentrations on admission were compared in order to differentiate complicated cases of acute pancreatitis from the mild course in 77 patients. Serum TNF concentration exceeded the detectable level only in seven of 77 patients (9 per cent), although complicated pancreatitis developed in 18 (23 per cent). The sensitivity and overall accuracy of TNF concentration in predicting severe disease were only 16 and 74 per cent respectively. The corresponding values for CRP (concentrations greater than 100 mg/l) were 84 and 74 per cent respectively. These data suggest that, in contrast with CRP, the early determination of peripheral blood TNF concentration is of no clinical value in assessing the severity of acute pancreatitis.

Acute Disease↗
PubMed1995

Characterization and radiosensitivity of UT-EC-2A and UT-EC-2B, two new highly radiosensitive endometrial cancer cell lines derived from a primary and metastatic tumor of the same patient.

UT-EC-2A was established from a patient with moderately differentiated Stage III endometrial adenocarcinoma with squamous metaplasia. UT-EC-2B was established from the same patient 17 months later from a metastasis in the left supraclavicular fossa. The origin of these cell lines was confirmed by DNA identity testing. Nude mice tumors produced by UT-EC-2A and UT-EC-2B cells recapitulated the histology of the original human tumors. Flow cytometric DNA contents of both primary and metastatic human tumors as well as corresponding nude mice tumors were diploid. The S-phase fractions of both cell lines were > or = 30%. The UT-EC-2A cell line was cytogenetically normal. The UT-EC-2B cell line had quite simple karyotype at low passage with an extra i(18p) and a deletion 21q, but at higher passages an additional three-way translocation 5;14;19 was observed. Radiosensitivity of the cell lines was tested with the 96-well plate clonogenic assay. The areas under the survival curves corresponding to the mean inactivation doses of UT-EC-2A and UT-EC-2B were 0.65 +/- 0.10 and 0.60 +/- 0.06 Gy, respectively. Measured survival at 2.0 Gy (SF2) was 0.042 for UT-EC-2A, 0.044 for UT-EC-2B, and 0.2 for skin fibroblasts. These cell lines are among the most radiosensitive human cancer cell lines described in the literature. Studying the characteristics of primary and metastatic cells derived from the same patient provides an opportunity to evaluate tumor progression.

Adenocarcinoma↗
PubMed1995

Comparison of cellular radiosensitivity between different localizations of head and neck squamous-cell carcinoma.

The prognosis of carcinomas arising from various sites in the head and neck varies even when the stage of the disease is taken into consideration, e.g. laryngeal carcinoma has a more favourable prognosis compared to oral-cavity malignancies. The purpose of this study was to evaluate intrinsic cellular radiosensitivity as one possible explanation for the observed differences in the survival rates of different anatomical groups. The radiation survival curves were determined for well characterized cell lines derived from laryngeal carcinoma (n = 14), pharyngeal carcinoma (n = 6), carcinoma of the oral cavity (n = 14) and the skin of the face (n = 3). The intrinsic radiosensitivity was expressed as area under the survival curve (AUC) values, and this cellular parameter was compared with clinical data and survival of the patients. The intrinsic radiosensitivity in the whole group varied between 1.0 Gy and 2.8 Gy with an average of 1.9 Gy. The mean AUC values for the laryngeal cell lines were 2.0 Gy +/- 0.2, for the oral cavity 1.8 +/- 0.3 Gy, for the pharynx 1.8 +/- 0.2 Gy and for cutaneous carcinoma 2.1 +/- 0.1 Gy. There was a slight difference between the groups of glottic and supraglottic cell lines (mean 1.8 +/- 0.2 Gy and 2.1 +/- 0.3 Gy, respectively), which is consistent with the differences in clinical curability of these cancers. Otherwise, the differences in cellular radiosensitivity of the carcinoma groups studied did not reach statistical significance. These results indicate that the intrinsic radiosensitivity of squamous-cell carcinoma (SCC) of the larynx does not significantly differ from that of SCC of other sites of the head and neck. Variations in the intrinsic radiosensitivity do not as such seem to explain the observed differences in radiocurability of SCC variously localized in the head and neck.

Carcinoma, Squamous Cell↗
PubMed1995

Increased serum pancreatitis associated protein (PAP) concentration after longterm alcohol consumption: further evidence for regular subclinical pancreatic damage after heavy drinking?

It has been shown recently that longterm but not short term heavy drinking of alcohol frequently results in increased serum activities of pancreatic enzymes suggesting subclinical pancreatic injury. Serum pancreatitis associated protein (PAP) is a novel protein, whose synthesis in the acinar cells and release into serum is specifically induced by acute pancreatic damage. This study was performed to further characterise the alcohol induced subclinical pancreatic injury by using serum PAP measurements. Three groups were studied: (1) control group (n = 25), (2) short term drinking group (n = 20), who consumed 2.0 g of ethanol per kg body weight during four hours, and (3) longterm drinking group (n = 32), who were admitted to withdrawal clinic after a median 30 months heavy drinking period. Serum PAP concentration was low in the control group (8 (5 to 12) micrograms/l, geometric mean (95% confidence intervals)). In the short term drinking group serum PAP was in the range of the control group values during 56 hours after drinking. Longterm drinking induced at least a 10-fold increase in serum PAP, the highest concentrations being seen on day 2 after drinking had ended (106 (61 to 184) micrograms/l). The patients did not develop abdominal symptoms, increased blood white cell count, or increased serum C reactive protein concentration. These results further support the suggestion that heavy longterm drinking often induces subclinical pancreatic damage, but not clinical pancreatitis.

Acute Disease↗
PubMed1994

Blood tests for detection of alcoholic cause of acute pancreatitis.

We investigated the ability of various blood markers to detect an alcoholic cause of acute pancreatitis. Serum carbohydrate-deficient transferrin (CDT) was significantly correlated with reported 2 month and 7 day ethanol consumptions and was significantly higher in 42 patients with alcoholic acute pancreatitis and in 24 patients with possibly alcoholic acute pancreatitis than in 20 patients with non-alcoholic disease. At a cutoff over 17 U/L, the specificity of CDT was 100% and the sensitivity was 75% to detect an alcoholic cause of acute pancreatitis. The lipase/amylase ratio index, erythrocyte mean corpuscular volume, and gamma glutamyl transferase could not distinguish alcoholic from non-alcoholic acute pancreatitis.

Acute Disease↗
PubMed1994

Acute pancreatic injury in asymptomatic individuals after heavy drinking over the long-term.

Recently, high-dose short-term alcohol exposure has been observed not to induce acute pancreatic damage, as evaluated by serum pancreatic enzyme activities. In this study the effect of high-dose, long-term alcohol exposure on the pancreas was investigated in 32 consecutive alcoholics admitted to a unit to treat the problems of withdrawal after a long period of heavy drinking. None of the alcoholics complained of abdominal symptoms. The signs of clinical acute pancreatitis (pain, increased serum C-reactive protein concentration or blood white cell count) were not observed in any of the alcoholics. A significant increase in serum total amylase, pancreatic isoamylase and lipase activities developed by the second day after termination of alcohol intake. These enzyme activities remained significantly increased for one week after cessation of drinking. Seven alcoholics had signs of chronic pancreatitis at ultrasonography (pancreatic calcification, pseudocyst). These results suggest that heavy alcohol intake over the long term may frequently induce subclinical pancreatic injury.

Acute Disease↗
PubMed1994

Amount of alcohol is an important determinant of the severity of acute alcoholic pancreatitis.

BACKGROUND: Does the amount of recently consumed alcohol correlate with the severity of acute alcoholic pancreatitis? METHODS: One hundred one consecutive episodes of acute pancreatitis (AP) were prospectively studied. Seventy-three were alcoholic AP episodes; 40 patients had their first alcoholic AP episode. A standard personal interview was used to determine the alcohol consumption during 2 months and during 1 week before AP. The severity of AP was evaluated according to the Ranson criteria, the serum C-reactive protein (CRP) concentration measured 24 to 48 hours after admission, the length of the hospital stay, the development of complications, and the mortality rate. RESULTS: In the 40 patients having their first alcoholic AP episode, the reported 2-month alcohol consumption correlated significantly with the number of positive Ranson criteria (correlation coefficient r = 0.44, p < 0.01), serum CRP concentration (r = 0.51, p < 0.001), and the length of the hospital stay (r = 0.45, p < 0.01). Complications occurred in eight of 14 patients with 2-month alcohol consumption of more than 5000 gm as compared with one of 14 patients with consumption of less than 2000 gm (p < 0.05). In the same 40 patients the 1-week alcohol consumption correlated with the number of positive Ranson criteria (r = 0.40, p < 0.05) and serum CRP concentration (r = 0.37, p < 0.05). Of the 12 patients who had consumed more than 1000 gm alcohol during the last week before admission, two died and complications developed in six (50%), as compared with none (p < 0.05) and six (21%), respectively, of those who had consumed less than 1000 gm. No significant correlations were observed between the reported alcohol consumption and any of the severity parameters in the 33 patients with recurrent episodes of alcoholic AP. CONCLUSIONS: The amount of alcohol consumed may be an important determinant of the severity of the first alcoholic AP episode but not of recurrent alcoholic AP.

Acute Disease↗
PubMed1993

Pancreatitis in Finland between 1970 and 1989.

The incidence and mortality from pancreatitis in Finland between 1970 and 1989 were studied and compared with the alcohol consumption in the country and with the incidence of liver cirrhosis and gall stone disease. Hospital discharge data were obtained from the Finnish National Agency for Welfare and Health, the causes of deaths from the Finnish State Statistics, and annual alcohol consumption from the Finnish State Alcohol Company. There were 56,353 hospital treatment periods because of pancreatitis. The incidence of pancreatitis discharges increased from 46.6 to 73.4/100,000/year. In men it increased from 59.1 to 113.4, but in women it remained unchanged (mean 35.0). The incidence of pancreatitis discharges correlated with the alcohol consumption in Finland (r = 0.78, p = 0.0001). The incidence of pancreatitis discharges correlated in men, but not in women, with the incidence of liver cirrhosis (r = 0.81, p = 0.0001). In women, but not in men, the incidence of pancreatitis discharges correlated with the incidence of gall stone disease discharges (r = 0.77, p = 0.0001). The incidence of discharges due to haemorrhagic pancreatitis and pancreatic abscess doubled in men and remained unchanged in women. Pancreatitis death rate decreased from 5.9% (men 4.8%, women 7.0%) to 2.6% (men 2.4%, women 2.7%).

Acute Disease↗
PubMed1992

Effect of a high dose of ethanol on serum pancreatic enzymes in young healthy adults.

Short-term effects of a high dose of ethanol on the serum activities of pancreatic enzymes were studied in young healthy adults. There were 10 males and 10 females in the study group, and two males and three females in the control group. In the study group, ethanol (2 g/kg of body weight) was given during 4 h, resulting in the blood ethanol level of 1.6 +/- 0.3 g/l at 6 h. No significant changes in serum pancreatic enzyme activities were observed in the control group during the 56-h experiment. In the study group, none of the individuals demonstrated a marked increase (double from the baseline) in serum pancreatic enzyme activities. In the male study group, the serum total amylase activity increased slightly at 6 h, but the serum pancreatic isoamylase activity remained unchanged. These data suggest that, in nonalcoholic individuals, short-term exposure to a high dose of ethanol does not induce such injury in the pancreas that would appear as a leak of enzymes from the acinar cells into the circulation.

Adult↗
PubMed1988

C-reactive protein in early detection of bacteremic versus viral infections in immunocompetent and compromised children.

The value of quantitatively determined C-reactive protein (CRP), measured from a finger prick sample for rapid detection of septicemia, was examined in 76 blood culture-positive infections in 54 immunocompetent and 18 compromised children; 73 patients with systemic viral infections served as controls. Development of a positive CRP reaction was also studied in 40 cases of acute epiglottitis. Beyond the neonatal age, an increased CRP value (greater than or equal to 20 mg/L) was found in 60 of 64 (94%) children with a positive blood culture for bacteria or fungus. By contrast, CRP remained below this value in 56 of 73 (77%) with viral infections. The immunologic status did not influence the CRP response. However, time had a highly significant (p less than 0.001) effect on CRP; a history of 6 to 12 hours of illness was required before CRP increased above normal. We conclude that CRP is a sensitive and rapidly reacting index in bacteremic infections. However, because other factors than septicemia also increase CRP, we deem a negative CRP value most informative; if two determinations taken several hours apart are less than 20 mg/L, the patient is very unlikely to have invasive bacterial infection.

Adolescent↗
PubMed1988

Serious bacterial infections. C-reactive protein as a serial index of severity.

The clinical course of 72 septicemic episodes or focal severe bacterial infections was monitored by daily measurements of serum C-reactive protein (CRP) in 59 children beyond the neonatal period, 19 of whom were immunocompromised. CRP was determined quantitatively by an immunoturbidimetric method from a finger prick sample until either clinical recovery occurred and antimicrobial therapy was discontinued or until the death of the patient. The primarily elevated CRP levels (greater than or equal to 20 mg/l) usually increased about for a day but then decreased rapidly, provided the patient recovered uneventfully. If not, CRP remained at a high level or reincreased after transient decrease. Behaviour of CRP was not affected by the immunologic status of the patient. This property makes CRP especially useful in immunocompromised patients in whom other commonly used laboratory parameters may fail.

Adolescent↗
PubMed1987

Frequency and functional characterization of specific T-helper cells infiltrating rat kidney allografts during acute rejection.

T-helper cells (ThC) play an important role in the induction of both cytotoxic T-cell responses and B-cell responses against the grafted organ. Furthermore, ThC alone are capable of causing graft rejection in T cell-deprived mice and rats. In view of these observations we found it important to analyse the frequency and functions of donor-specific ThC in the allograft and in the recipient lymphoid system during the course of acute renal allograft rejection. A limiting dilution assay was developed which, due to the absence of exogenous interleukin 2 (IL-2) and the low numbers of stimulator cells used, appears to be highly selective for the proliferation of specific ThC. Kidney transplants were performed from LBN (RT1n) to congenic Lewis (RT1l) strain differing in major histocompatibility complex (MHC) only. The inflammatory (white) cells were recovered from the graft, and blood and recipient spleen and the frequency of RT1n-responding ThC were determined at different times after transplantation. In the kidney graft itself, the frequency of ThC responding to RT1n MHC antigens was 1:3000 on day 2 and increased to 1:670-1320 at the peak of inflammation. In the spleen, the frequency increased from 1:1000 on day 0 to 1:200 on day 8, and remained high even after the graft was rejected. In the blood, the frequency stayed at the 1:400-1:800 level, and increased to 1:200 only after the graft had been completely destroyed. Individual ThC clones deriving from limited dilution assays of kidney and spleen cells were recovered and expanded with irradiated donor cells without IL-2 and finally with exogenous IL-2 only. All clones showed the T-helper (W3/25) phenotype, seven out of eight tested clones showed a specific anamnestic response to RT1n alloantigens and no response to RT1l or RT1a in a secondary MLC, 12 out of 12 clones produced IL-2 and 11 out of 11 clones produced gamma interferon upon re-stimulation with relevant allogeneic cells, and eight out of ten clones collaborated with syngeneic B cells for Ig synthesis, indicating that they were indeed derived from specific ThC and/or from their precursors. Taken together, the results demonstrate that specific ThC and/or their precursors represent only a very small minority in the graft-infiltrating inflammatory population. This makes it most unlikely that the ThC themselves are responsible for graft destruction; the results indicate rather that a major role of ThC in situ may be instruction of immunologically specific and nonspecific components of inflammation.

Animals↗