Howard B. Hamilton

Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California: Demographic, physical, dietary and biochemical characteristics

CORONARY heart disease and stroke continue to be the subjects of intensive epidemiologic study in many parts of the world. Particular research interest has been focused on the apparent differences in the prevalence and incidence of coronary heart disease among various racial and geographically separate population groups [l-4]. As a result of these intensive efforts to explain the epidemiology of these diseases and to determine methods of control, pioneering studies have established risk factors for coronary heart disease [.5-lo] and are now establishing such risk factors for cerebrovascular disease as well [l 1, 121. At present, multifactorial causation has been accepted, the strongest evidence being the demonstrated relationship between elevated blood lipid levels, elevated blood pressure levels, and heavy cigarette smoking with coronary atherosclerosis and its clinical manifestations [5-10, 13-161. Studies in many countries have shown that in most populations exhibiting a high serum cholesterol in men, there is also a high prevalence of coronary heart disease [17-191. Usually these people eat a diet high in fat, especially in the form of meat and dairy fat. In most populations with low cholesterol levels and a low prevalence of coronary heart disease, the intake of fat is low and the fat which is ingested is derived primarily from fish and vegetable oils [ 17-201.

Thyroid disease: a study in Hiroshima, Japan.

The relation of thyroid disease to single, whole-body exposure to ionizing radiation was studied in matched samples of exposed and non-exposed subjects residing in Hiroshima, Japan. Clinical investigations were conducted on 169 patients with thyroid disease, of whom 152 were females. It was concluded that a number of etiological factors are significant in the production of simple goiter. Carcinoma of the thyroid was diagnosed in 12 patients. Although a greater number of malignancies were seen among the most heavily exposed, differences among distance groups was not statistically significant.

The frequency in Japanese of genetic variants of 22 proteins. I. Albumin, ceruloplasmin, haptoglobin, and transferrin.

This paper presents the results of an electrophoretic survey of approximately 4000 individuals from the cities of Hiroshima and Nagasaki, Japan, for four serum proteins: albumin, ceruloplasmin, haptoglobin and transferrin. The haptoglobin gene frequencies obtained for the HP1‐HP2 polymorphism are in agreement with earlier reports. Rare electrophoretic variants of albumin, ceruloplasmin and haptoglobin occur with frequencies of 2.48, 0.50 and 0.58 per 1000 determinations, respectively. The noteworthy finding of 8 distinct transferrin variants in these populations, with a combined frequency of 20.90 per 1000 determinations, is also presented. Four of these variants (DCh1, B1, B3 and Dhir2 which corresponds electrophoretically to D4) have been reported in other populations in Japan, but the other five have not previously been differentiated.

Peripheral lymphocyte response to PHA and T cell population among atomic bomb survivors

The percentage of T lymphocytes of atomic bomb survivors showed no change as a function of age or exposure dose. The percentage of T cells was slightly lower in malignant-tumor patients than in the control group, but was significantly higher in the group with chromosomal aberrations than in the control group. The percentages of phytohemagglutinin (PHA)-induced transformation of peripheral lymphocytes decreased significantly with age in the 0 rad control group and the 200+ rad exposure group, particularly so in the latter. The malignant-tumor group also showed lower percentages of PHA-induced transformation than the control group. The percentages of PHA-induced transformation of lymphocytes of the chromosomal-aberration group were significantly depressed as compared with that of the control group.

Hemoglobin Hiroshima (β143 histidine → aspartic acid): a newly identified fast moving beta chain variant associated with increased oxygen affinity and compensatory erythremia

During a survey for hemoglobinopathies in over 9000 residents of Hiroshima Prefecture, Japan, a fast moving hemoglobin was identified in eight members of three generations in a Japanese family. The abnormal hemoglobin, named Hb Hiroshima, constitutes about 50% of the total hemoglobin in hemolysates from the carriers who have a mild erythremia but are otherwise apparently clinically unaffected. All preparations of Hb Hiroshima have increased affinity for oxygen, by either tonometric or oxygen electrode determinations. At pH 7.0, the oxygen pressure, P(50) required to half saturate an unfractionated hemolysate from a carrier was one-half that of Hb A, and the P(50) of a purified sample containing no Hb A was one-fourth that of Hb A. The pH dependence of the oxygen equilibrium (Bohr effect) is below normal, as shown by the absolute value of the Bohr effect factor which is about half that of Hb A, in the pH range between 7.0 and 7.4. The Hill constant, n, for Hb Hiroshima between pH 7.0 and 7.4 is 2-2.4, compared to 2.8-3 for Hb A under the same conditions, indicating reduction of, but not complete abolition of heme-heme interaction. Urea dissociation and canine hybridization tests located the biochemical lesion in the beta chain. Fingerprints (Ingram), carboxypeptidase digestion, and amino acid analysis demonstrated that the substitution was at residue 143 in the beta chain, where histidine was replaced by aspartic acid.In contrast to other recently described high oxygen affinity mutants that show intact Bohr effects, all three of the major characteristics of the reversible combination of hemoglobin with oxygen (oxygen equilibrium, heme-heme interaction, and pH dependence) are affected in Hb Hiroshima. A tentative interpretation of these effects, relating structure to function, is offered in terms of recently developed models of normal hemoglobin.

Rheumatoid arthritis and gout in Hiroshima and Nagasaki, Japan. A prevalence and incidence study.

Abstract Observations of definite rheumatoid arthritis in a fixed population of 11,393 atomic bomb survivors in Hiroshima and Nagasaki for the period April, 1965 through December, 1966, based on a prospective study designed for specific detection of rheumatoid arthritis are reported. Routine complete physical examinations were performed on all persons in the sample. Screening procedures utilized in all subjects included: completion of a questionnaire and performance of ‘rheumatoid factor’ tests. When indicated by results of clinical and laboratory examinations, PA roentogenograms of the hands and wrists were obtained. A rheumatologist (ID) reviewed the medical records of all individuals in whom there was evidence to suspect rheumatoid arthritis. 1303 of individual patients whose earlier examinations indicated the need, were recalled for clarification, confirmation and classification of their disease. The time of onset of disease was also established. The prevalence rate of definite rheumatoid arthritis was 0.38 per cent for males and 0.65 per cent for females, over 20 years of age, and 0.55 per cent for both sexes. This prevalence rate for females was significantly lower than the age adjusted rate in a comparable population in Tecumseh, but this was not so for males. The incidence rate of definite rheumatoid arthritis was 0.07 per cent for males and 0.11 per cent for females per year. In this sample of Japanese, the prevalence rate of positive latex tube fixation tests for the rheumatoid factor was consistently higher than reported for the comparable Tecumseh, Michigan, population. Adequate explanation of this difference is not now available. The relationship between rheumatoid arthritis or rheumatoid factor and environmental factors such as education, occupation, and other physical findings such as level of serum uric acid and blood pressure was studied. No relationship was detected between prevalence and incidence of rheumatoid arthritis and exposure to radiation from the atomic bombs. The age-sex specific mean uric acid values for Japanese men and women were very similar to those in a Caucasian population. In this population survey, as reported in others, very few cases of gout were detected.

Carrier State in Human Acatalasemia

The heterozygous carrier state of a rare hereditary disease, acatalasemia, has been defined biochemically. Affected homozygotes have no blood catalase activity, whereas heterozygotes show activities intermediate between this inactivity and the activity of normal controls, without overlap. Pedigrees show a high frequency of consanguineous marriages.

Hemoglobin Hijiyama: A New Fast-Moving Hemoglobin in a Japanese Family

A variant of hemoglobin A, named Hb Hijiyama, found in two generations of a Japanese family living in Hiroshima, Japan, has a higher anodal electrophoretic mobility than hemoglobin A; a gain of two negative charges per molecule is indicated. Fingerprinting and amino acid analysis showed the biochemical anomaly to be in the beta chain at residue 120, where lysine is replaced by glutamic acid. In the heterozygote carriers of the abnormal hemoglobin there is no apparent association with clinical or hematologic abnormalities.

Immunochemical studies on catalase: II. An anticatalase reacting component in normal, hypocatalasic, and acatalasic human erythrocytes

Abstract Quantitative precipitin studies coupled with immunochemical techniques have identified in normal human erythrocytes a minor component of catalase which, though reacting with rabbit antihuman catalase serum, lacks enzyme activity. Hemolyzates from presumed carriers (heterozygotes) of the gene for acatalasia also show the minor component, though the quantity of the active enzyme itself is reduced. Preparations from acatalasic (homozygotic) individuals contain only the minor inactive component. Purification by Sephadex gel filtration shows the minor component to have a molecular weight about one sixth of the fully constituted active enzyme. There is no Soret absorption. The authors postulate the minor component to be a subunit or precursor of catalase, or both. Based on these findings, a possible genetic interpretation of the defect in human hereditary acatalasia is offered.

Susceptibility of Anopheles stephensi to Plasmodium gallinaceum: a trait of the mosquito, the parasite, and the environment.

Background Vector susceptibility to Plasmodium infection is treated primarily as a vector trait, although it is a composite trait expressing the joint occurrence of the parasite and the vector with genetic contributions of both. A comprehensive approach to assess the specific contribution of genetic and environmental variation on “vector susceptibility” is lacking. Here we developed and implemented a simple scheme to assess the specific contributions of the vector, the parasite, and the environment to “vector susceptibility.” To the best of our knowledge this is the first study that employs such an approach. Methodology/Principal Findings We conducted selection experiments on the vector (while holding the parasite “constant”) and on the parasite (while holding the vector “constant”) to estimate the genetic contributions of the mosquito and the parasite to the susceptibility of Anopheles stephensi to Plasmodium gallinaceum. We separately estimated the realized heritability of (i) susceptibility to parasite infection by the mosquito vector and (ii) parasite compatibility (transmissibility) with the vector while controlling the other. The heritabilities of vector and the parasite were higher for the prevalence, i.e., fraction of infected mosquitoes, than the corresponding heritabilities of parasite load, i.e., the number of oocysts per mosquito. Conclusions The vectors genetics (heritability) comprised 67% of “vector susceptibility” measured by the prevalence of mosquitoes infected with P. gallinaceum oocysts, whereas the specific contribution of parasite genetics (heritability) to this trait was only 5%. Our parasite source might possess minimal genetic diversity, which could explain its low heritability (and the high value of the vector). Notably, the environment contributed 28%. These estimates are relevant only to the particular system under study, but this experimental design could be useful for other parasite-host systems. The prospects and limitations of the genetic manipulation of vector populations to render the vector resistant to the parasite are better considered on the basis of this framework.