Human and humans

A number of chimerized, humanized, and one human mAb have now been approved for therapeutic use in humans in the treatment of autoimmunity, malignancy, infection and cardiovascular disease (Table 1). Some of the currently licensed mAb will be discussed here. A much larger number of mAb are currently being evaluated in Phase I, II and III trials. In general, chimeric, humanized and human mAb are very well tolerated with few side effects. Chimeric or humanized mAb still have the potential to evoke host immune response to the variable domains or CDRs of the antibody so-called HACA (human anti-chimeric antibody) or HAHA (human anti-human antibody) responses, although these responses are uncommon. Short-lived and occasionally severe infusion-related acute hypersensitivity reactions such as fever, skin itching, shivering, respiratory compromise and low blood pressure sometimes occur-. Such effects may... 

Isophorone produced kidney effects in male rats in the NTP (1986) study. Strasser (1988) found that isophorone caused protein droplet formation in the kidneys of male rats, suggesting that isophorone can induce protein nephropathy. Alden (1986) discussed the possibility that proteinuric humans and humans with low molecular weight protein nephropathy, such as people with multiple myeloma (Bence-Jones protein) or mononuclear cell leukemia (lysozyme), may be more susceptible to chemically-induced protein nephropathy. He concluded, however, that this syndrome is probably specific to the male rat. 

Schramm DD, Wang JF, Holt RR, Ensunsa JL, Gonsalves JL, Lazarus SA, Schmitz HH, German JB, Keen CL. 2001. Chocolate procyanidins decrease the leukotriene-prostacyclin ratio in humans and human aortic endothelial cells. Am J Clin Nutr 73 36-40. 

From the baseline information, C02, VOCs and ventilation rate profiles have been identified. Although the levels do not generally exceed local threshold levels (ENV, 1996), it is important to understand how these profiles come to be, what their potential effects on sensory perception and health may be, what emission strengths they have and how they may be apportioned to various sources such as humans and human-related activities, building materials and the ventilation system. 

Fig. 3.3 Classes of monoclonal antibodies. Upper panel The different classes of monoclonal antibodies (murine, chimeric, humanized and human, with typical suffixes in the compound names). Lower panel Murine fractions of different classes are illustrated, with declining immunogenicity of the decreasing murine fractions.

It is forecast that up to the end of the current decade, the research focus regarding therapeutic mAbs will be on two categories oncology and arthritis, and inflammatory and immune disorders. A significant increase of sales is expected up to 2008 for chimeric mAbs, in absolute terms, and for human and humanized mAbs, in relative terms (Figure 16.2). Up to now, murine mAbs are those with the lowest approval rate (4.5%), whereas the chimeric are the most successful (26%). The approval rates for humanized mAbs (18%) and human antibodies (14%) were intermediate. However, as most of the last two types are still under development, the approval situation may change significantly in the future (Reichert and Pavlou, 2004). 

Science is human and human beings are a muddle. In his book The Periodic Table, Primo Levi referred to chemistry as a mess compounded of stenches, explosions, and small futile mysteries. There too he distinguished two conflicting philosophical conclusions. The one he called the praise of purity, which protects from evil like a coat of mail. The other he referred to as the praise of impurity, which gives rise to changes, in other words, to life. So, he continued, take the solution of copper sulfate which is in the shelf of reagents, add a drop of it to your sulfuric acid, and you ll... 

Anthropological archaeology Archaeological investigations that seek to answer the larger, fundamental questions about humans and human behavior taught in departments of anthropology. 

Fig. 2.1 Diagram showing the proportion of human (green) and murine (red) sequences in mouse, chimeric, humanized and human antibody structures, as exemplified by HuCAL...

That a number of the chimeric, humanized and human biopharmaceuticals in Table 2.1 are highly successful drugs proves that the movement away from murine monoclonals towards antibodies of more human composition has paid dividends in the clinic. The conclusion for drug development is that antibodies that are predominantly human in their composition are less likely to encounter problems of immunogenicity than murine antibodies. 

This difference between murine antibodies and those comprising some human content is also evident in overall developmental success rates. Data from the Tufts Centre for the Study of Drug Development [11] show that the probabilities of chimeric, humanized or fully human antibodies progressing from entry into cHnical trials to the market are 26, 18 and 14%, respectively, while for murine antibodies the corresponding probability is only 4.5%. Caution should be used in drawing any conclusions from the apparently higher success rates in developing chimeric over humanized and human antibodies since the sample size is limited to those 17 antibodies which had reached the market at the time the study was performed. 

For this reason, we pay close attention to minimizing sources of error. Examples of common sources of error might be contamination or an improperly mixed buffer. In addition, one should remember that scientists are humans, and human error is always a possibility. 

The earth is rich in hostile environments. These include a wide array of natural systems deep-sea vents, salt brines, thermal pools, volcanic lakes, and frigid ice fields. Others are anthropogenic, often the result of extractive hard rock, oil or coal mining. Nobel laureate Paul Crutzen suggested that we are currently living in the anthropocene , an era in which humans and human activities have become a major geological force on the planet [11]. Whether man-made or natural, extreme environments can harbor life forms called extremophiles. 

Speech-processing technology has been a mainstream area of research for more than 50 years. The ultimate goal of speech research is to build systems that mimic (or potentially surpass) human capabilities in understanding, generating and coding speech for a range of human-to-human and human-to-machine interactions. 

In academic and industry laboratories, modern genetic engineering continues to solve problems related to health, disease, industry, and sericulture. Additional apphcations in humans and human... 

Hoc, J.-M., and Lemoine, M.-P. 1998. Cognitive evaluation of human-human and human-machine cooperation modes in air traffic control. International Journal of Aviation Psychology, 8(1), 1-32. 

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