Oligomerization of hamster UDP-GlcNAc:dolichol-P GlcNAc-1-P transferase, an enzyme with multiple transmembrane spans

Hamster UDP-GlcNAc:dolichol-P GlcNAc-1-P transferase (GPT), which initiates N-linked glycosylation by catalyzing the synthesis of GlcNAc-P-P-dolichol, has multiple transmembrane spans and a catalytic site that probably exists on the cytosolic face of the endoplasmic reticulum membrane (Dan, N., Middleton, R. M., and Lehrman, M. A. (1996) J. Biol. Chem. 271, 30717-30725). In this report, we demonstrate that GPT forms functional oligomers, probably dimers. Oligomers were detected by chemical cross-linking of GPT and by a dominant-negative effect caused by co-expression of enzymatically inactive (but properly folded) GPT mutants. The GPT mutants had no effect on two other dolichol-P-dependent endoplasmic reticulum enzymes. Mixing experiments indicated that mature GPT was competent for oligomerization. Oligomerization appeared to be favored in detergent extracts compared with intact microsomes. Detergent treatments were found to prevent, rather than promote, nonspecific aggregation of GPT. These results demonstrate that GPT subunits can physically interact and influence each other. The implications of oligomerization for enzyme function are discussed. From these results, we conclude that GPT is one of a very small number of multitransmembrane span enzymes that can form multimers.     

The effect of the herbicide Dinoseb-acetate (Aretit) on transaminase (GOT, GPT) activity in the blood serum and muscles of the Japanese quail (Coturnix coturnix japonica)

An experiment was undertaken to study the effect of the dinoseb-acetate (Aretit) herbicide, administered in drinking water at a concentration of 100 and 200 mg x 1(-1) for four days, on the activity of transaminases (GOT and GPT) in the blood serum and muscle of the Japanese quail (Coturnix coturnix japonica). GOT had higher activity values in the blood serum and muscle of the control and test birds, as compared with GPT. The herbicide increases GOT activity in the blood serum, whereas the GPT value remains unchanged. In muscle, the activity of GOT decreases as a result of the action of dinoseb-acetate and GPT activity remains unchanged. Under in vitro conditions, dinoseb-acetate (concentrated 0.01 to 1000 mg x 1(-1)) increases GOT activity in the blood serum and muscle, GPT activity remaining the same. It is assumed that transaminases are specifically involved in the adaptation mechanisms of the animals to dinoseb-acetate intoxication.     

The effectiveness of preservation of hepatic arterial blood flow by modified Appleby procedure with reconstruction of the hepatic artery--serial changes in postoperative liver function

We investigated whether modified Appleby procedure with reconstruction of the hepatic artery can avoid complications due to a decrease in heptic arterial flow which has been comprehended in conventional Appleby's operation. The postoperative liver function of 17 patients undergoing modified Appleby's procedure was compared with that of 16 patients undergoing total gastrectomy and distal pancreato-splenectomy (control group). (1) Anticoagulant therapy was not required during and after operation. The common hepatic arterial flow after vascular anastomosis was 396 +/- 101 ml/min. Postoperative celiac arteriography revealed good patency of anastomosis. (2) There were no significant differences between the modified Appleby group and the control group in any of the blood levels of GOT, GPT total bilirubin and alkaline phosphatase at any point until the fourth postoperative week. In none of the patients in the modified Appleby group, the blood levels of GOT and GPT exceeded 250 IU/l. (3) In the modified Appleby group, ICG-R15 was 4 +/- 1% before operation and 6 +/- 3% at the first postoperative month. These results suggested that modified Appleby procedure enabled us to perform resection according to Appleby's operation safely, without need for preoperative or intraoperative examination about the retrograde blood flow mediated by the gastrodudenal artery.     

Selective outgrowth and differential tropism of amacrine and photoreceptor axons to cell targets during early development in vitro

Plastids of nongreen tissues import carbon as a source of biosynthetic pathways and energy. Within plastids, carbon can be used in the biosynthesis of starch or as a substrate for the oxidative pentose phosphate pathway, for example. We have used maize endosperm to purify a plastidic glucose 6-phosphate/phosphate translocator (GPT). The corresponding cDNA was isolated from maize endosperm as well as from tissues of pea roots and potato tubers. Analysis of the primary sequences of the cDNAs revealed that the GPT proteins have a high degree of identity with each other but share only approximately 38% identical amino acids with members of both the triose phosphate/phosphate translocator (TPT) and the phosphoenolpyruvate/phosphate translocator (PPT) families. Thus, the GPTs represent a third group of plastidic phosphate antiporters. All three classes of phosphate translocator genes show differential patterns of expression. Whereas the TPT gene is predominantly present in tissues that perform photosynthetic carbon metabolism and the PPT gene appears to be ubiquitously expressed, the expression of the GPT gene is mainly restricted to heterotrophic tissues. Expression of the coding region of the GPT in transformed yeast cells and subsequent transport experiments with the purified protein demonstrated that the GPT protein mediates a 1:1 exchange of glucose 6-phosphate mainly with inorganic phosphate and triose phosphates. Glucose 6-phosphate imported via the GPT can thus be used either for starch biosynthesis, during which process inorganic phosphate is released, or as a substrate for the oxidative pentose phosphate pathway, yielding triose phosphates.     

Activity of some serum enzymes in calves suffering from white muscle disease

The paper described the findings of the activity of aspartate amino transferase (GOT) and alanine amino transferase (GPT), lactate dehydrogenase (LDH), alkaline phosphatase (AP), and aldolase in the blood serum of calves examined for white-muscle disease (WMD). Relapsing mass accurrence of the disease was reported from various agricultural enterprises where calves were fed a milk replacer without vitamin E. In comparison with clinically healthy calves fed a feed mixture with vitamin E, calves suffering from the clinical form of WMD showed an alkaline phosphatase level decrease from 32.3 +/- 7.6 u. K. A. to 15.1 +/- 8.2 u. K. A. On the other hand, the activites of ALD, GOT, GPT, and LDH showed a statistically significant increase. The acute and sub-acute course of the disease increased enzyme activities as follows: ALD from 4.2 +/- 1.1 mumol (= 70.0 +/- 17.0 i.u.) to 9.7 +/- 2.1 mumol (= 163.0 +/- 33.2 i. u.), GOT from 0.9 +/-0.5 mumol (= 68.0 +/- 5.8 i.u.) to 16.7 +/- 11.7 mumol (= 567.0 +/-40.0 i. u.) GPT from 0.2 +/- 0.8 mumol (= 5.0 +/- 12.4 i. u.) to 9.8 +/- 2.8 mumol (= 330.0 +/- 40.4 i.u.), LDH from 46.1 +/- 5.4 mumol (= 765.0 +/- 40.0 i.u.) to 72.7 +/- 24.3 mumol (= 1,207.0 +/- 403.0 i.u.). In WMD-affected herds, similar enzyme activity fluctuations were observed even in calves showing no clinical signs of the disease. It follows from the study that the examination of serum enzymes provides a method to demonstrate the clinical and pre-clinical forms of white-muscle disease and that it can be included in the set of tests for the diagnosis of diseases in calves. The significant differences in all calves in the affected herds show that the disease is a danger to all animals in the herd fed a deficient mixture.     

Santolindiacetylene, a polyacetylene derivative isolated from the essential oil of Santolina canescens

The yield, composition, and some pharmacological activities (hepatoprotective and antioxidant) of the essential oil of Santolina canescens aerial parts have been investigated. The essential oil qualitative data were determined by gc and gc-ms. The main component, santolindiacetylene [1], was isolated and characterized by spectral methods, and the structure assigned as 1-(2'-naphthyl)hexa-2,4-diyne. The protective activities of the essential oil and its main component [1] were evaluated against carbon tetrachloride-induced hepatotoxicity in a rat model. In both cases a significant hepatoprotective effect was observed, as evident from the strong decrease of elevated GPT serum levels caused by carbon tetrachloride-induced hepatic damage.     

Some blood parameters of water buffalo in different physiological conditions

The Authors have studied the changes of GOT, GPT, ALP, CPK and Se in buffaloes under different physiological conditions (age, diet, different pre and post partum times). 99 adult buffaloes were classified in 8 groups on the basis of different pre, post partum time intervals. Moreover, other 39 animals were divided into 4 groups: A = 60-90 day old animals, fed with reconstituted milk supplemented with Vit E; B = same age, fed with maternal milk; C = 6-8 month old animals; D = 12-18 month old animals. In the various classes of animals blood ALP, GPT, GOT, CPK and Se were monitored. Results showed that the high variability in blood activity of the studied enzymes suggest that in establishing their reference values the physiological condition of the subject and the time interval from the parturition must be taken into account. The fact that Se was not detectable in many pregnant animals suggests that the prevention of myodistrophy in buffalo calves must be effected in prenatal epoch.     

Bacteriological, pharmacokinetic and clinical evaluation of azithromycin in the pediatric field]

Azithromycin (AZM), a new macrolide antibiotic, in fine granules and in capsules was studied for pharmacokinetic and clinical evaluation in the pediatric patients. Antibacterial activity of AZM against 43 clinical isolates: AZM exhibited slightly lower activity against Gram-positive bacteria and 2-8-fold higher activity against Gram-negative bacteria than erythromycin or clarithromycin. Plasma or urine samples were collected from eight patients receiving the drug in fine granular form, and two patients receiving it in capsules for the determination of drug levels. The elimination half-lives of AZM after administration at dose of 10 mg/kg/day for 3 days were 50.0 and 51.2 hours for fine granules, and 41.5 hours for capsules. AUC0-infinity was 11.7 and 24.3 micrograms.hr/ml for fine granules, and 8.3 micrograms.hr/ml for capsules. The cumulative excretion rates up to 120 hours after the start of treatment were 8.24 and 13.84% for fine granules, and 3.83% for capsules. AZM was administered to 123 patients once daily at 3.7-20.0 mg/kg body weight over 3 to 5 days with reference to the standard dose of 10 mg/kg. The drug was used to treat patients with pharyngitis, tonsillitis, scarlet fever, pneumonia, mycoplasmal pneumonia, chlamydial pneumonia, otitis media, pertussis, intestinal infection, and SSTI. The effectiveness of AZM was evaluated in 109 cases. The drug was rated "excellent" in 65.1% of the patients and "good" in 29.4%, resulting in an efficacy rate of 94.5%. Furthermore, AZM eradicated 43 of 46 (93.5%) bacteria that had been identified before the treatment. Three patients complained of side effects of urticaria (1 case) and diarrhea (2 cases). Abnormal laboratory changes were reported as follows: decreased leukocyte (3 cases), increased eosinophil (5), increased platelet (2), increased eosinophil and platelet, elevated GPT (1), and elevated GOT and GPT (1). The abnormalities, however, were mild enough to raise no clinically significant problems. In conclusion, AZM in once daily regimen was effective and safe in treatment of pediatric infections.     

How to control the blood glucose level in the surgical diabetic patient

Plasma activities of lactic dehydrogenase (LDH), creatine phosphokinase (CPK), glutamic pyruvic transaminase (GPT), and alkaline phosphatase (ALP) were studied, along with hematological changes, in rats suffering from various degrees of experimental decompression sickness (DS). By 1 h after decompression, LDH and CPK activities were elevated in moderate and severe DS whereas GOT and GPT were elevated only in severe DS. ALP was reduced in all decompressed rats. Hematological changes indicated hemoconcentration, the degree of which paralleled the severity of DS. By 24 h after decompression, all enzyme activities were approaching control levels with the exception of GOT, which was further elevated from the 1-h value. The observed lung damage in rats with severe DS in conjunction with the hematologic and enzyme data suggested that hypoxemic-hypoxia, incident to bubble embolization of pulmonary vasculature, was a major factor in altering the blood enzyme pattern in DS. Serum enzyme data from two inadequately decompressed divers are also reported.     

Potency comparison of peptidomimetic inhibitors against HIV-1 and HIV-2 proteinases: design of equipotent lead compounds

The results of investigation of haptoglobin (Hp) types in 596 donor blood samples in some towns of Ukraine (Dnepropetrovsk, Kharkov, Odessa, Kiev, Uzhgorod, Zhitomir) are presented. Three normal Hp types (Hp1-1, Hp2-1 and Hp2-2) have been found. The reliable interpopulation differences in the Hp types frequency were not found. On the whole the Hp types frequency in the type Hp1-1 comprised 12.7%. In the type Hp2-1-48.1% and in the type Hp2-2-36.5%. The frequency of the gene Hp1 is 0.38. The frequency of the Hp types and of the gene Hpl in Ukraine is similar to that in population of Eastern Europe and European Part of Russia.     

Psychological testing for child and adolescent psychiatrists: a review of the past 10 years

Vibrio cholerae O1 strains isolated mostly in Japan between 1977 and 1995 were typed according to restriction fragment patterns by cleavage of genomic DNA with Sfi I and Not I and separation by Pulsed-field gel electrophoresis (PFGE). Two hundred sixty five strains from human were divided into 60 PFGE patterns (provisional types). Strains of type 2-3, 3-4, 4-5 and 51-54 were dominant in the Philippines, Thailand, India and Indonesia, respectively. Types 1-1, 2-3, 2-53, and 3-4 were detected over a long period of time in contrast to the other types. Strains of the same type (Types 1-1, 2-3, 2-53 and others) isolated from the Japanese who had never been outside Japan were often found among strains from Southeast Asia. Most strains from humans were cholera-toxin (CT)-positive, while those from the environment and the sea were generally not. 23 strains from the environment and the sea in Japan were divided into 12 types. Strains of the same types as CT-positive strains from humans could not be found in the environment and sea. These results suggest that cholera in Japan is closely related with cholera in Southeast Asia and PFGE is useful for epidemiological analysis of cholera in Japan.     

Influence of pretreatment with carbon tetrachloride on paracetamol-induced hepatotoxicity

The influence of preventive treatment with a low dose of carbon tetrachloride on paracetamol-induced hepatotoxicity was evaluated in the rat. The haloalkane was given intraperitoneally (200 microliter/kg) 48 hours prior to paracetamol (PRCT; 2000 mg/kg, os). In parallel groups of rats were treated with CCl4 or PRCT alone. Twelve hours after paracetamol all the animals were killed. Liver damage was determined by evaluating total lipid and triglyceride accumulation in hepatic tissue and the serum activity of alanine-amino transferase (S.GPT). In addition, both the hepatic concentration of reduced glutathione (GSH) and the production "in vitro" of TBA-reacting compounds by liver homogenate were assayed. The results obtained indicate CCl4 "per se" induces a significant triglyceride accumulation but does not influence either the hepatic GSH level or the leakage of GPT into the blood stream. In addition, the haloalkane does not stimulate the production of TBA-reacting substances by hepatic tissue. Paracetamol, alone, produces a slight increase of hepatic triglycerides while induces a significant (+ 108%) enhancement of S.GPT activity. The drug is also able to stimulate the lipid peroxidation "in vitro", whereas provokes a marked decrease of GSH in liver tissue. Combined treatment with the two poisons results in a minor alteration of hepatocyte function as shown by the lack of GPT in serum and by the reduced fall of hepatic GSH as well as by a decreased production of TBA-reacting compounds. In our opinion, CCl4 partially protects against paracetamol-induced liver injury by interacting with enzymes which are responsible for the biotransformation of PRCT to a reactive arylating species that bind to cell molecules.     

Incidence and demographic correlates of depressive symptoms during pregnancy in an inner London population

We evaluated the relationship between the area under the concentration versus time curve (AUC) of cyclosporin A (CsA) and several other clinical factors, because the clinical utility of AUC monitoring has been ambiguous. Fifty-four clinical time courses from 14 Japanese renal transplant patients during hospitalization, in the period from April 1990 to March 1997, were examined. In a bivariate regression analysis there was no correlation between the AUC and the daily dose of CsA (mg/kg/day) when the individual data or total series data were analyzed. In a chi-square test, the donor type of kidney (chi(2) = 25.254, df = 1, p = 0.0000) and renal function-related episodes, i.e. acute tubular necrosis, hemodialysis, hypertension, nephrotoxicity, or rejection (chi(2) = 13.982, df = 1, p = 0.0002) directly affected posttransplant renal function assessed by creatinine clearance, while episodes of hepatic function as assessed by the glutamate-pyruvate transaminase (GPT) activity level had no correlation with the posttransplant renal function evaluated according to creatinine clearance. In contrast, the renal function-related episodes significantly affected the AUC after renal transplantation (chi(2) = 4.934, df = 1, p = 0.0263), while hepatic function assessed by GPT did not. In a multivariate analysis, the creatinine clearance and obesity had significant positive correlations with the AUC, whereas the hematocrit had a significant negative correlation with the AUC. From these observations, we concluded that the dosage adjustment of CsA cannot be performed using the linear relationship between the daily oral dose and the AUC, and that renal function, obesity, and the CsA blood distribution properties affect the CsA pharmacokinetics after renal transplantation. Posttransplant renal function as well as obesity and CsA blood distribution properties are important factors to be considered when therapeutic monitoring is performed.     

A comparative study of guinea pig and rat tracheal reactivity

Species differences in behavior and responses of guinea pig (GPT) and rat (RT) tracheal smooth muscle to electrical field stimulation (EFS) and chemicals were investigated under semi-isometric conditions. Indomethacin augmented and papaverine reduced the contractions elicited by EFS in both tissues. They relaxed the GPT and did not affect the tone decline in the RT. Experiments with different load, cartilage content, thread and rubber strips suggest the role of elastic elements in passive elongation of the RT. This was independent of muscarinic, adrenergic, histaminergic and serotoninergic receptors, nitric oxide, eicosanoids and metabolic processes. The second response on repeated administration of acetylcholine was augmented and that of serotonin attenuated in both GPT and RT. Upon repeated elevation of [K+]o the tissues responded in an opposite manner. Further data are provided on similarities (modulation of cholinergic transmission by prostaglandins, sensitization to acetylcholine and desensitization to serotonin) and differences (innervation, responses to repeated elevation of [K+]o, presence/absence of prostaglandin-regulated basal tone and spontaneous activity) in reactivity of GPT and RT.     

Frequency, diagnosis, and course of hepatotoxic side effects of Rifampicin (author's transl)

In a retrospective study the following was found: Out of 111 patients suffering from tuberculosis and receiving a combined INH-therapy without Rifampicin 23% showed an increase of serum-transmainase activities, on the other hand out of 105 patients, treated with a combination including Rifampicin 74% did so. A pathological De Ritis ratio GOT/GPT was found in 31 among 59 comparable cases of Rifampicin-treated patients, and a pathological ratio GOT + GPT/AP in 22 among 37 cases before the transaminase-activities rose above normal. Development of a distinct toxic hepatic damage has to be anticipated in those cases, which show a De Ritis ratio below 0,5 or a GOT + GPT/AP ratio above 1,0 while transaminase-activity still is only slightly elevated. Liver biopsies taken from 10 patients showed no regular relation to the biochemical data.     

Studies on the efficacy and safety of biapenem (L-627) against infections in pediatrics

The efficacy and the safety of biapenem (L-627), a new carbapenem antibiotic, against infections in pediatrics were studied. The obtained results are summarized as follows. 1. L-627 at dose levels of 5.4 mg/kg to 12.4 mg/kg (daily doses of 16.2 mg/kg to 37.2 mg/kg) was administered by intravenous drip infusion 3 times daily for 5 to 7 days to 2 cases of pneumonia, 3 cases of skin and soft-tissue infections and 1 case of urinary tract infection for a total of 6 cases. As results, all the cases showed good or better responses including 4 excellent and 2 good results. Bacteriological efficacies in all of the 3 eligible cases were assessed as "eradicated". 2. As for the safety, a decrease in the WBC count and slight elevation of GOT and GPT were observed in 1 case as abnormal changes in the laboratory tests results, only incidence of side effect observed was the eruption in 1 case. 3. The results above indicate that L-627 is useful for the treatment of general infections in pediatrics.     

Increased portal endothelin-1 level is associated with the liver function after cardiopulmonary bypass in rabbits: influence of hypothermia on the damage

The purpose of this study was to prove the hypothesis that ET-1 production is increased in the splanchnic-hepato circulation during cardiopulmonary bypass (CPB) with or without hypothermia and this greatly affects hepatocellular function after surgery. Twelve Japanese white rabbits were used. In group I (n = 6), the rectal temperature was kept at 37.0 degrees C during CPB (90 min). In group II (n = 6), the rectal temperature was lowered to 26 degrees C during the first 30 minutes and then increased to 37 degrees C for the following 60 minutes. In group I, surface liver tissue blood flow (LBF) remained stable during CPB. While, in group II, LBF was significantly reduced to 66.9% of baseline values during hypothermic CPB, but it increased during the rewarming phase to 84.3% of the baseline value (p = 0.0070). At the end of CPB, portal ET-1 levels were increased in both groups, but they were significantly higher in group II (7.32 +/- 0.50 pg/ml and 9.29 +/- 0.61 pg/ml, respectively). Serum GOT, GPT, LDH and arterial ammonia levels were also higher in group II. Portal ET-1 levels had a significant positive correlation with those liver enzymes. Histopathological examination after CPB showed severe damage of the hepatic parenchyma in zone 3 associated with microvesicular fatty infiltration in group II.     

Pharmacokinetic, bacteriological and clinical evaluation of tazobactam/piperacillin in pediatrics

Pharmacokinetic, bacteriological and clinical studies were performed in pediatrics on tazobactam/piperacillin (TAZ/PIPC), a combined drug of a new beta-lactamase inhibitor tazobactam and piperacillin at a ratio of 1:4. 1. Serum levels and urinary excretions of TAZ, PIPC and desethyl piperacillin (DEt-PIPC), a metabolite of PIPC, after one shot intravenous administration of 50 mg/kg of TAZ/PIPC to two children (6-7 years old) were investigated. The serum TAZ level at 0.08 hour was 50.8-51.0 micrograms/ml after administration. Then TAZ concentrations gradually decreased with half-lives of 0.38-0.45 hour, and reached 1.0-1.4 micrograms/ml after 2 hours and was not detected after 3 hours and 6 hours. Serum PIPC levels at 0.08 hour was 167.0-231.0 micrograms/ml after administration. Then PIPC concentrations gradually decreased with half-lives of 0.41-0.55 hour, and reached 1.2-2.4 micrograms/ml after 3 hours and was not detected after 6 hours. DEt-PIPC was detected slightly in serum. A ratio of TAZ to PIPC was about 1 to 4 in serum at each time. Urinary recovery rates of TAZ in the first 6 hours after administration of TAZ/PIPC were 33.5-90.1% and those of PIPC were 41.9-77.8% and those of DEt-PIPC were 1.5-2.8%. 2. TAZ/PIPC was administered to 27 pediatric patients (their ages ranged between 2 months and 11 years old) with various infections, and clinical and bacteriological effects and adverse reactions were investigated. Single doses were 26.2-55.6 mg/kg, frequencies of administration were 3-4 times a day, and durations of administration were 3 1/3-7 1/3 days, and total dosages were 4.5-33.75 g. Clinical effects were evaluable in 26 cases. Responses were rated as "good" in acute purulent tonsillitis 1 case and acute purulent otitis media 1 case, as "excellent" in acute sinusitis 1 case, as "excellent" in 2 and "good" in 1 out of 3 cases of acute bronchitis, as "excellent" in 13 and "good" 2 out of 15 cases of acute pneumonia, as "excellent" in acute urinary tract infection 2 cases and as "excellent" in acute enteritis in 1 case, acute appendicitis in 1 case and lymphadentis in 1 case. In all cases, the results were rated as "good" or "excellent". Antimicrobial effects against a total of 10 strains identified or assumed to be pathogenic bacteria were evaluated. The 10 strains of bacteria included 4 strains of Streptococcus pneumoniae, 3 strains of Haemophilus influenzae (2 strains beta-lactamase producing), 2 strains of beta-lactamase producing Moraxella catarrhalis, 1 strain of beta-lactamase producing Morganella morganii. All the bacteria listed here were judged to have been eradicated. Adverse reaction was observed in 1 case with mild diarrhea. As abnormal changes in laboratory data, leucocytopenia in 1 case, elevation of GOT. GPT in 2 cases and eosinophilia in 1 case were observed. On the basis of the findings, TAZ/PIPC was considered to be effective and safe in the treatment of pediatric infections.     

Age-related dynamics of the genetic marker distribution in an irradiated population. Haptoglobin genetic system

The age dynamics of haptoglobin (Hp) type and allele distribution was studied in 985 workers aged 35-79 years who worked in the atomic industry. These workers were exposed to chronic radiation in a wide range of doses 17-40 years ago. Along with the chi 2 test, the relative and attributive risks of elimination of Hp types and alleles were determined to obtain the qualitative characteristics of age alterations. The substantial changes in distribution of Hp types and alleles were revealed in individuals older than 60 years. These changes depended on doses of external and internal irradiation. For instance, in individuals of this age group, who received the total dose of gamma-radiation (less than 100 cGy) and or that of plutonium-239 incorporation (less than 1.48 kBq), a decrease in Hp 2-2 and Hp2 and an increase in Hp 1-1 and Hp1 was observed. However, among the individuals of similar age (older than 62 years), who received a higher total dose of external and/or internal radiation, the different Hp type distribution showed a decrease in Hp 2-1 and an increase in Hp 1-1. In the latter case, the changes with age were dose-dependent. In individuals over 60 years of age with essential hypertension or diabetes mellitus and those who had a myocardial infarction, a decrease in Hp 2-2 and Hp2 and an increase in Hp 1-1 and Hp1 were found. This explains the changes with age in individuals irradiated at lower doses. The peculiar changes with age in individuals irradiated at higher doses are possibly due to the difference in morbidity and mortality from malignancy in various Hp type carriers.