Molecular cloning and sequence analysis of cDNA encoding human ferrochelatase

The cDNA encoding human ferrochelatase [EC 4.99.1.1] was isolated from a human placenta cDNA library in bacteriophage lambda gt11 by screening with a radiolabeled fragment of mouse ferrochelatase cDNA. The cDNA had an open reading frame of 1269 base pairs (bp) encoding a protein of 423 amino acid residues (Mr. 47,833) with alternative putative polyadenylation signals in the 3' non-coding regions and poly (A) tails. Amino acid sequencing showed that the mature protein consists of 369 amino acid residues (Mr. 42,158) with a putative leader sequence of 54 amino acid residues. The human enzyme showed an 88% identity to mouse enzyme and 46% to yeast enzyme. Northern blot analysis showed two mRNAs of about 2500 and 1600 bp for ferrochelatase in K562 and HepG2 cells. As full-length cDNA for human ferrochelatase is now available, molecular lesions related to erythropoietic protoporphyria can be characterized.     

Light and electron microscopical combined staining by immunohistochemical and enzyme histochemical methods using rat prolactin-secreting pituitary tumours

Summary Combined immunohistochemical staining (IHCS) and enzyme histochemical staining (EHCS) methods for light microscopy (LM) and electron microscopy (EM) are reported, using oestrogeninduced rat pituitary tumours. For LM, combined staining for alkaline phosphatase and acid phosphatase by EHCS, using the azo dye method, and for prolactin and ACTH by IHCS, using the enzyme-labelled antibody method, gave the best results on 1 m glycol methacrylate sections. For EM, combined staining by EHCS on 30 m tissue sections followed by IHCS for prolactin on ultrathin Epon sections (enzyme-labelled antibody method) provided acceptable results. By these combined staining methods, the neoplastic prolactin cells were shown to have close affinity to rich alkaline phosphatase-positive capillaries and to possess an alkaline phosphatase-positive cell membrane. Furthermore, they revealed acid phosphatase-positive lysosomal and secretory granules. These combined staining methods may be valuable in studies on the actual functional status of cells.     

A population genetic study on the transition from Jomon people to Yayoi people

In the study on the origin of Japanese, one of main unsolved problems is the transition from the Jomon people to the Yayoi people. The main difficulty in solving this problem has been the lack of suitable skeletal materials belonging to the time between the two periods, i.e. the final Jomon and the early Yayoi Periods. Therefore, we know few details of the transition period. It is important to know who carried out a drastic change of the Yayoi culture during this transitional period, i.e. the native Jomon people or the immigrant people. By introducing population genetic models, we show that a view that the immigrant people had a significant genetic contribution to the origin of Japanese is compatible with results from anthropological and archeological studies. This result implies that the immigrant people were mainly responsible for the drastic cultural change during the transitional period.     

The evolution of conformist transmission in social learning when the environment changes periodically

Conformity is often observed in human social learning. Social learners preferentially imitate the majority or most common behavior in many situations, though the strength of conformity varies with the situation. Why has such a psychological tendency evolved? I investigate this problem by extending a standard model of social learning evolution with infinite environmental states (Feldman, M.W., Aoki, K., Kumm, J., 1996. Individual versus social learning: evolutionary analysis in a fluctuating environment. Anthropol. Sci. 104, 209-231) to include conformity bias. I mainly focus on the relationship between the strength of conformity bias that evolves and environmental stability, which is one of the most important factors in the evolution of social learning. Using the evolutionarily stable strategy (ESS) approach, I show that conformity always evolves when environmental stability and the cost of adopting a wrong behavior are small, though environmental stability and the cost of individual learning both negatively affect the strength of conformity.     

Estimating hominid life history: the critical interbirth interval

Unlike any great apes, humans have expanded into a wide variety of habitats during the course of evolution, beginning with the transition by australopithecines from forest to savanna habitation. Novel environments are likely to have imposed hominids a demographic challenge due to such factors as higher predation risk and scarcer food resources. In fact, recent studies have found a paucity of older relative to younger adults in hominid fossil remains, indicating considerably high adult mortality in australopithecines, early Homo, and Neanderthals. It is not clear to date why only human ancestors among all hominoid species could survive in these harsh environments. In this paper, we explore the possibility that hominids had shorter interbirth intervals to enhance fertility than the extant apes. To infer interbirth intervals in fossil hominids, we introduce the notion of the critical interbirth interval, or the threshold length of birth spacing above which a population is expected to go to extinction. We develop a new method to obtain the critical interbirth intervals of hominids based on the observed ratios of older adults to all adults in fossil samples. Our analysis suggests that the critical interbirth intervals of australopithecines, early Homo, and Neanderthals are significantly shorter than the observed interbirth intervals of extant great apes. We also discuss possible factors that may have caused the evolutionary divergence of hominid life history traits from those of great apes.     

Birth rate and mortality rate of infants with congenital malformations of the limbs in the Awajishima free-ranging group of Japanese monkeys (Macaca fuscata)

The birth rate and mortality rate of infants with congenital malformations of the limbs were examined in the Awajishima free-ranging group of Japanese macaques (Macaca fuscata). Of the 606 infants born between 1978 and 1995, 86 (14.2%) were malformed. The male-female ratio did not differ between malformed and normal infants. Most kin-groups included females who gave birth to malformed infants at least once. The mortality rate within the first year after birth for malformed infants (28.2%) was significantly higher than that for normal infants (10.0%). However, this indicates that more than 70% of malformed infants were able to survive for the first year of life, even though they were unable to cling to their mothers ventrum due to their limb deformities. This finding indicates that maternal care-taking is sufficient to enable malformed infants to survive during the early stages of development and that clinging by the infant is not necessary for the display of maternal care. Am. J. Primatol. 42:225–234, 1997. © 1997 Wiley-Liss, Inc.     

The effect of trauma on Neanderthal culture: A mathematical analysis

Traumatic lesions are often observed in ancient skeletal remains. Since ancient medical technology was immature, severely traumatized individuals may have frequently lost the physical ability for cultural skills that demand complex body movements. I develop a mathematical model to analyze the effect of trauma on cultural transmission and apply it to Neanderthal culture using Neanderthal fossil data. I estimate from the data that the proportion of adult individuals who suffered traumatic injuries before death was approximately 0.79–0.94, in which 0.37–0.52 were injured severely and 0.13–0.19 were injured before adulthood. Assuming that every severely traumatized individual and a quarter to a half of the other traumatized individuals lost the capacity for a cultural skill that demands complex control of the traumatized body part, I estimate that if an upper limb is associated with a cultural skill, each individual had to communicate closely with at least 1.5–2.6 individuals during adulthood to maintain the skill in Neanderthal society, and if a whole body is associated, at least 3.1–11.5 individuals were necessary. If cultural transmissions between experts and novices were inaccurate, or if low frequency skills easily disappeared from the population due to random drift, more communicable individuals were necessary. Since the community size of Neanderthals was very small, their high risk of injury may have inhibited the spread of technically difficult cultural skills in their society. It may be important to take this inhibition into consideration when we study Neanderthal culture and the replacement of Neanderthals by modern humans.     

Association of Patient Care with Ventilator-Associated Conditions in Critically Ill Patients: Risk Factor Analysis

BackgroundVentilator-associated conditions (VACs), for which new surveillance definitions and methods were issued by the Center for Disease Control and Prevention (CDC), are respiratory complications occurring in conjunction with the use of invasive mechanical ventilation and are related to adverse outcomes in critically ill patients. However, to date, risk factors for VACs have not been adequately established, leading to a need for developing a better understanding of the risks. The objective of this study was to explore care-related risk factors as a process indicator and provide valuable information pertaining to VAC preventive measures.MethodsThis retrospective, single-center, cohort study was conducted in the intensive-care unit (ICU) of a university hospital in Japan. Patient data were automatically sampled using a computerized medical records system and retrospectively analyzed. Management and care-related, but not host-related, factors were exhaustively analyzed using multivariate analysis for risks of VACs. VAC correlation to mortality was also investigated.ResultsOf the 3122 patients admitted in the ICU, 303 ventilated patients meeting CDC-specified eligibility criteria were included in the analysis. Thirty-seven VACs (12.2%) were found with a corresponding rate of 12.1 per 1000 ventilator days. Multivariate analysis revealed four variables related to patient care as risk factors for VACs: absence of intensivist participation in management of ventilated patients [adjusted HR (AHR): 7.325, P < 0.001)], using relatively higher driving pressure (AHR: 1.216, P < 0.001), development of edema (AHR: 2.145, P = 0.037), and a larger body weight increase (AHR: 0.058, P = 0.005). Furthermore, this research confirmed mortality differences in patients with VACs and statistically derived risks compared with those without VACs (HR: 2.623, P = 0.008).ConclusionFour risk factors related to patient care were clearly identified to be the key factors for VAC preventive measures.     

Molecular defect in human erythropoietic protoporphyria with fatal liver failure

We investigated the molecular basis of ferrochelatase in a Japanese patient with erythropoietic protoporphyria (EPP), complicated by fatal liver failure, and defined a novel point mutation in the ferrochelatase gene. cDNAs were synthesized using Epstein-Barr-virus-transformed lymphoblastoid cells from the proband. cDNA clones encoding ferrochelatase in the proband were isolated by amplification using the polymerase chain reaction. There were two sizes of ferrochelatase cDNAs; one was normal in size, the other being smaller. Sequence analysis of the abnormally sized cDNA clones revealed that they lacked exon 9 of the ferrochelatase gene. Genomic DNA analysis demonstrated that the proband had the abnormal allele and that it contained a G to A point mutation at the first position of the donor site of intron 9. An identical mutation was detected in the affected family members of the proband by allele-specific oligonucleotide hybridization analysis. EPP is inherited in an autosomal dominant manner in this family.