Showing papers on "Virus published in 1975"

Theiler's virus infection in mice: an unusual biphasic disease process leading to demyelination.

Abstract: An unusual biphasic central nervous system disease developed in 3-week-old Swiss outbred mice after intracerebral inoculation of the DA strain of Theiler's murine encephalomyelitis virus. Nine to 20 days postinfection 86% of mice became paralyzed, and approximately one-half of these animals survived. During this period neuronal necrosis and microglial proliferation were seen in thalamus, brainstem, and spinal cord. There was an initial phase of virus growth in spinal cord followed by persistent infection at a lower concentration. Virus antigen was readily found in the cytoplasm of neurons by immunofluorescent staining early in the course of infection, whereas after 30 days there was a paucity of cells containing virus antigen which were present only in the spinal cord white matter. Between 1 and 5 months, an intense mononuclear inflammatory cell lesion evolved in the spinal cord leptomeninges and white matter, which coincided with a mild gait disturbance in some surviving mice, and patchy demyelination was found in areas of inflammation. The acute gray matter pathology would appear to be the result of direct virus lytic effect. Although the late white matter lesion culminating in demyelination probably represents a cytocidal infection similar to the situation that exists in certain picornavirus carrier culture systems, a virus-induced immunopathological process merits further study.

Function of simian virus 40 gene A in transforming infection.

Abstract: In productive infection by simian virus 40, the A gene is known to regulate the initiation of viral DNA replication and to control the synthesis of late viral RNA. The function of the A gene in transforming infection was investigated by the infection of a variety of cell species with six independently isolated temperature-sensitive mutants belonging to the A complementation group. The A mutants failed to initiate the stable transformation of cells during continuous infection at the restrictive temperature. After the establishment of transformation at the permissive temperature and a subsequent shift to the restrictive temperature to block the A function, however, two distinct virus-cell interactions were identified. In one case, the increased colony-forming capacity of transformed cells remained stable after the temperature shift. In the other case, the temperature shift decreased the capacity of transformed cells to form colonies to the level of untransformed control cells. The outcome of the virus-cell interaction depended both on the nature of the A mutation in a given cell species and on the species of the cell transformed by a given mutant. These findings suggest that the transformation process may require two distinct events, each related to A gene expression.

Establishment and characterization of an Epstein-Barr virus (EBC)-negative lymphoblastoid B cell line (BJA-B) from an exceptional, EBV-genome-negative African Burkitt's lymphoma

Abstract: An Epstein-Barr virus (EBV)-negative lymphoblastoid cell line (LCL), BJA-B, was established from an African Burkitt's lymphoma (BL) which contained no detectable EBV DNA and did not express the EBV specified antigen EBNA, BJA-B cells grow in typically large, flat clumps. All carry surface-bound immunoglobulins, a B lymphocyte marker, and do not form rosettes with sheep erythrocytes. After infection of BJA-B cells by EBV the infected cells may produce either EBV-determined nuclear antigen (EBNA) or both EBNA and early antigen (EA), depending on the strain of EBV. The homogeneity of the BJA-B cell population with respect to immunological and isoenzyme markers and size suggests a clonal origin of the line. BJA-B is the first EBV-negative LCL established from an African Burkitt's lymphoma and demonstrates that an EBV-independent continuous B cell line can be established "in vitro" from other than leukemia or myeloma cells.

H-2 compatibility is required for t-cell-mediated lysis of target cells infected with lymphocytic choriomeningitis virus

Abstract: Maximal cell-mediated lysis of targets infected with lymphocytic choriomeningitis virus occurs only within a H-2 compatible system. Syngeneic immune spleen cells are at least 100 times as effective as are allogeneic lymphocytes. Reciprocal restriction of cytotoxic T-cell activity has been shown to operative between H-2k, H-2d, and H-2b. Experiments with cogenic mice have localized the effect to the H-2 gene complex. Furthermore, the observation that lymphocytes from H-2a mice cause high specific 51Cr release from either H-2d virus-infected cells, indicates that identity at either the K or the D end of the H-2 gene complex is sufficient for this lytic interaction.

Chromatin Structure: Deduced from a Minichromosome

Abstract: Cells lytically infected with simian virus 40 contain viral DNA in the form of very small chromlosomnes (minichromosomes) segmented into 100-A lengths, each segment containing about 200 base pairs of DNA. This form resembles that of eukaryotic chromnosom1es anid is consistent with the model of chromatin structure proposed recently.

Genetics of natural resistance to herpesvirus infections in mice.

Abstract: INHERITED resistance to virus infections has been demonstrated in several murine systems1–6. Susceptibility to mouse hepatitis virus3 and resistance to arbovirus7 infections in mice are dominant traits associated with the capacity of macrophages from the susceptible strains to replicate virus. Resistance to Friend leukaemia virus- and Gross leukaemia virus-induced leukaemogenesis is determined by at least two genes, one closely linked to the immune response genes of the mouse8. Conversely, susceptibility to lymphocytic choriomeningitis (LCM) virus infections in mice has been associated with a gene closely linked to the immune response genes9. The latter seems to be associated with the cell-mediated immune response to LCM which causes tissue damage and leads to death. Cell-mediated immunity seems to be important in resistance against herpes simplex virus (HSV) infections10–12. Analysis of the aspects of cell-mediated immunity which might be involved in resistance in man is complicated by the uncontrollable factors associated with activation of latent herpesvirus infections. I have developed a mouse model which has shown that at least three genes are responsible for resistance to HSV. Although preliminary evidence suggests that resistance is immunologically mediated, resistance genes do not seem to be closely linked to the histocompatibility region of the mouse.

Acute and recurrent infection with herpes simplex virus in the mouse: a model for studying latency and recurrent disease.

Abstract: Summary Nineteen recent isolates and three laboratory strains of herpes simplex virus types 1 and 2 were tested for their ability to produce clinical signs in mice following intradermal inoculation in the ear. All viruses produced erythema at the inoculation site; this was the most sensitive clinical sign of infection. Virus multiplication in the ear tissue was similar for both types 1 and 2 up to the fifth day after inoculation but type 2 viruses persisted for longer. Latent infection was demonstrated in cervical dorsal root ganglia. Type 1 viruses required a much higher dose than type 2 to produce neurological signs and death after intradermal inoculation but the difference was less after intracerebral inoculation. Erythema of the inoculated ear recurred sporadically during several months observation in about half the mice that survived intradermal infection with a selected type 1 isolate. The presence of virus in the ear tissue during such recurrences was confirmed by electron microscopy and isolation of infectious virus. The system of ear infection in the mouse is presented as a new model for studying neurovirulence, and latent and recurrent infection with herpes simplex virus.

Rat cell line 3y1 and its virogenic polyoma- and sv40- transformed derivatives.

Abstract: Cell lines were established from cultures derived from Fischer rat embryos according to the transfer schedule described by Todaro and Green (1963) for mouse 3T3 cells where cell crowding and serum exhaustion were kept to a minimum. Cell growth rate did not decline greatly during the course of successive 3-day transfers. Like 3T3 cells, the rat cell lines possess very low saturation densities under standard culture conditions. A clonal cell line with a relatively high plating efficiency was obtained from one of the cell lines, 3Y1. In these cloned cultures, virus growth was not detectable upon infection with SV40, while a small amount of virus was produced upon infection with polyoma virus. Morphological transformation of the cloned 3Y1 cells by SV40 and polyoma virus could be assayed with single-hit kinetics and with efficiencies comparable to those of the previously available transformation systems for each virus. Independent cell lines transformed by SV40 were consistently virus-free and all the lines tested produced SV40 upon fusion with permissive monkey cells. Most of the independent transformed cell lines isolated after polyoma infection appeared to be virus-free, although the cultures of some lines produced a small amount of polyoma virus spontaneously after a prolonged cultivation. Most of the virus-free polyoma-transformed lines produced virus upon fusion with permissive mouse cells.

Epidemiology of Cytomegalovirus Infection after Transplantation and Immunosuppression

Abstract: Viral infections and clinical complications were studied during hemodialysis and after renal transplantation. Active cytomegalovirus infection developed in 96% of patients after renal transplantation; reactivation of herpes simplex, varicella-zoster, and Epstein-Barr viruses was found in 35%, 24%, and 0% of patients, respectively. Cytomegalovirus viremia developed in 42% of patients an average of two months after renal transplantation, lasted 1.75 (+/- 1.5) months (except in one patient with chronic viremia), and was followed by chronic viruria. Higher titers of infectious cytomegalovirus were found in the polymorphonuclear than in the mononuclear leukocyte fraction. Reactivation of a latent infection and, less likely, respiratory infection appear to be the most probable mechanisms of cytomegalovirus infection after renal transplantation. One to three months after transplant, cytomegalovirus infection may be related to fever, arthralgia, pneumonitis, and leukopenia; three to four months after transplant, the virus may be related to hepatitis; and 12-30 months after transplant, it may be related to retinitis in patients with chronic viremia. Although other causes of these complications are possible, herpes simplex virus, Epstein-Barr virus, varicella-zoster virus, measles virus, adenovirus, hepatitis B virus, and Toxoplasma gondii appear to be of lesser importance than cytomegalovirus in this respect.

Methylated nucleotides block 5'-terminus of vaccinia virus messenger RNA.

Abstract: Studies on the nature and location of the methylated nucleotides in mRNA synthesized in vitro by vaccinia virus particles revealed an unusual 5'-terminal structure. Evidence that the pyrophosphate group is blocked by 7-methylguanosine and that both 2'-O-methyl-adenosine and 2'-O-methylguanosine occupy penultimate positions was presented. According to this model, the 5'-termini of vaccinia virus mRNAs are: 7MeG-5'ppp-5'GMepNp and 7MeG-5'AMepNp.

Simian virus 40 gene A function and maintenance of transformation.

Abstract: Transformants have been isolated after infection of rat embryo cells at 33 C with either wild-type simian virus 40 or with the temperature-sensitive gene A mutants, tsA7 and tsA28. Examination of properties usually associated with transformation such as growth in 1% serum, growth rate, saturation density, and morphology show that these properties are temperature dependent in the tsA transformants characterized, but are not temperature dependent in the wild-type transformants that have been examined. In the most thoroughly characterized tsA transformants the expression of T antigen also appears to be temperature dependent. These data suggest that an active A function is required for the maintenance of transformation in these cells. In the lytic cycle, the A function is involved in the initiation of DNA synthesis. Thus transformation by simian virus 40 may be the direct consequence of the introduction of the simian virus 40 replicon and the presence of its DNA initiator function, which causes the cell to express a transformed phenotype.

A blocked structure at the 5' terminus of mRNA from cytoplasmic polyhedrosis virus.

Abstract: METHYLATION of a specific nucleotide occurs at the initial stage of transcription of the double-stranded RNA genome in cytoplasmic polyhedrosis virus (CPV) in the presence of the methyl-group donor, S-adenosyl methionine (SAM)1. Methylation of mRNA has been reported recently not only for other viruses2,3 but also for a mouse L-cell4. Since methylation seems to be coupled with the initiation of mRNA synthesis in CPV, the structure of the initiation (5′) terminus of mRNA transcribed from CPV by the virus-containing RNA polymerase is of particular interest.

Studies on the primary structure of the influenza virus hemagglutinin

Abstract: The amino-terminal sequence and composition of the subunits of the hemagglutinin (HA) of influenza virus has been determined. The hemagglutinin has been isolated by two techniques. (1) as the intact hemagglutinin after disruption of the virus in sodium dodecyl sulfate, giving 2 subunits of 58,000 daltons (HA1) and 26,000 daltons (HA2), and (2) after treatment of the virus with bromelain, giving 2 subunits of 58,000 daltons (BHA1) and 21,000 daltons (BHA2). In both preparations these subunits are linked by disulfide bonds. The aminoterminal sequences of HA1 and BHA1, and HA2 and BHA2 are the same. The composition of the 50 residue peptide associated with the membrane, which is removed from the C-terminus of HA2 by bromelain, is deduced and shown to be hydrophobic and contain 50% of the serine residues of HA2. The biosynthetic precursor of the hemagglutinin has been purified from the membranes of abortively infected chick fibroblasts and shown to have the same amino terminus as HA1. Thus the order of biosynthesis is NH2-HA1-HA2-COOH. The amino-terminal sequence of BHA2--at the cleavage site of the precursor--is shown to be a palindrome: NH2-Gly-Leu-Phe-Gly-Ala-Ile-Ala-Gly-Phe-Ile-. This sequence is conserved in representative viruses from each of the major pandemics. A region of homologous sequence is described between the hemagglutinins of influenza type A and B viruses.

Direct transformation of 3T3 cells by Abelson murine leukaemia virus.

Abstract: MURINE leukaemia viruses (MLV) cause tumours of haemopoietic origin in vivo1,2, but although they replicate in vitro, they generally do not transform cells. MLV provides helper activity3 for the replication of defective murine sarcoma virus (MSV)4 which possess a transforming activity5. Abelson and Rabstein6 isolated an agent in association with Moloney leukaemia virus (MLV-M) which causes a rapidly progressive lymphoblastic leukaemia of bone-marrow-derived lymphocytes (B cells)7. In addition, this Abelson virus (MLV-A) in conjunction with MLV-M causes rapid appearance of immunoglobulin-producing plasmacytomas in BALB/c mice primed with oil8. We now report that MLV-A can be defective for virus replication and show that this agent directly transforms 3T3 cells in vitro. A quantitative transformation assay is described.

In vitro transformation of lymphoid cells by Abelson murine leukemia virus

Abstract: Cell cultures prepared from fetal murine liver were infected by Abelson murine leukemia virus After about 2 weeks, proliferating cells of lymphoid morphology appeared in some of the cultures Addition of 2-mercaptoethanol to the initial culture medium greatly enhanced the appearance of the lymphoid cells Immunoglobulin determinants were evident on the cells in some cultures Continuous passage of the cells in certain cultures was possible and the passaged cells could form tumors after animal inoculation Because Abelson murine leukemia virus is able to induce in vitro malignant transformation of lymphoid cells, it probably causes leukemia by directly affecting cellular growth control

The Epstein-Barr Virus and Neoplasia

Abstract: Epstein–Barr virus (EBV) is a lymphotropic herpes virus in man.1 Its main target is the human B lymphocyte.2 Only B lymphocytes and most if not all B lymphocytes have specific EBV receptors.3 Recent evidence suggests that the complement receptor of the B lymphocyte is either identical or closely associated with EBV receptor (Jondal M, Klein G, Oldstone MB: unpublished data). EBV can convert normal lymphocytes, which have a limited life span in vitro, into permanently growing cell lines.4 5 6 7 8 9 Such "immortalized" lines have a diploid or near-diploid karyotype,10 carry multiple copies of the viral genome per cell11 12 13 14 and express EBV-specific nuclear . . .

Immune and Antibody Responses to an Isolated Capsid Protein of Foot-and-Mouth Disease Virus

Abstract: The purified capsid proteins VP1, VP2, and VP3 of foot-and-mouth disease virus type A12 strain 119 emulsified with incomplete Freund's adjuvant were studied in swine and guinea pigs. Swine inoculated on days 0, 28, and 60 with 100-μg doses of VP3 were protected by day 82 against exposure to infected swine. Serums from animals inoculated with VP3 contained viral precipitating and neutralizing antibodies, but such serums recognized fewer viral antigenic determinants than did antiviral serums. Capsid proteins VP1 and VP2 did not produce detectable antiviral antibody in guinea pigs, and antiviral antibody responses in swine to a mixture of VP1, VP2, and VP3 were lower than the responses to VP3 alone. However, when swine were inoculated with VP1, VP2, and VP3 separately at different body sites, no interference with the response to VP3 was observed. Vaccine containing VP3 isolated from acetylethylenimine-treated virus appeared less protective for swine than vaccine containing VP3 from nontreated virus. Trypsinized virus, which contains the cleaved peptides VP3a and VP3b rather than intact VP3, produced approximately the same levels of antiviral antibody responses in guinea pigs as did virus. Conversely, an isolated mixture of VP3a and VP3b did not produce detectable antiviral antibody responses in guinea pigs. The VP3a-VP3b mixture did, however, sensitize guinea pigs to elicit such responses following reinoculation with a marginally effective dose of trypsinized virus.

Genes required for cytotoxicity against virus-infected target cells in k and d regions of h-2 complex.

Abstract: EVIDENCE is mounting that in mice, certain specific immunological effector functions of thymus-derived (T) lymphocytes are efficient only when donors of T cells and the cells with which they interact have at least a part of the H-2 gene complex in common1–8. Examples include T helper function in vivo and in vitro1–3, cytotoxicity mediated by T cells against virus-infected4–6 or TNP-modified7 target cells in vitro, immunopathology mediated by T cells4, or protection against bacterial8 and viral infection6 in vivo. This requirement for H-2 compatibility has been studied in detail by measuring the cytotoxicity of T cells from donors immunised with either lymphocytic choriomeningitis (LCM) or ectromelia virus using target cells infected with the homologus virus.

Pathogenesis of of cytomegalovirus infection. I. Activation of virus from bone marrow-derived lymphocytes by in vitro allogenic reaction.

Abstract: After infection in utero or at birth with a cell culture adapted strain of mouse cytomegalovirus (MCMV), several mouse strains developed a latent virus infection in the presence of specific antiviral antibodies. Up to 5 mo after infection, MCMV could be activated and recovered from spleen lymphocytes of the infected animals that were co-cultivated with histoincompatible (H-2 foreign) mouse embryo cells from uninfected animals. In contrast, co-cultivation of lymphoid cells from infected mice with mouse embryo cells from syngeneic, histocompatible (H-2 similar) donors did not activate MCMV. Similarly, MCMV was not recovered from sonicated lymphoid cells. Virus was activated by treating viable lymphoid cells with lipopolysaccharide, a B-cell mitogen, but was not activated by a variety of other mitogens such as phytohemagglutinin, concanavalin A, or pokeweed mitogen. Subsequent purification of lymphoid cells from the infected mice by a variety of techniques indicated that MCMV was harbored in the B-lymphocyte population.

Clinically Useful Method for the Isolation of Respiratory Syncytial Virus

Abstract: A simple method for the isolation of respiratory syncytial virus (RSV) is reported; it is relatively rapid and results in a high frequency of recovery of virus. A nasal secretion specimen with high titers of virus is inoculated at the bedside onto susceptible cell lines to avoid loss of viral infectivity due to liability of the virus. During an outbreak of RSV, viral specimens were obtained by this method from all young children admitted to the hospital with lower respiratory tract disease. RSV or influenza A virus was recovered from 89% of these 45 children. RSV was isolated from 87% of those with pneumonia. RSV was recovered 60% less often from specimens obtained simultaneously by conventional nasopharyngeal swabs. Identification of RSV cytopathic effect was more rapid with use of the bedside nasal wash method and was accomplished in an average of four days. Hence, this information was available to the clinicician when it was still useful in the management of the patient's illness.

Seroepidemiology of human papovaviruses discovery of virgin populations and some unusual patterns of antibody prevalence among remote peoples of the world

Abstract: A total of 1544 sera from 28 diverse and mainly isolated populations were examined for HI antibody to BK virus. A few extremely isolated populations were found with negligible or absent exposure to the virus, but in most populations, remote or cosmopolitan, antibody appeared in increasing prevalence during early childhood and remained stable throughout adult life. Antibody acquisition and prevalence rates in individual families reflected that of the general population. Examined for HI antibody to JC virus were 393 sera from 9 of the 28 populations. Age acquisition and prevalence rates of antibody were similar to those of BK virus, but experience with the 2 viruses was found to occur independently in several population groups, i.e., high exposure to BK with low exposure to JC, or vice-versa. Examined for neurtralizing antibody to SV40 were 151 sera with and without BK HI antibody in individuals from several primitive populations. SV40 antibody, mainly in low titer, occurred in 35% of the BK-positive group, but only 5% of the BK-negative group, suggesting that infection with BK or a closely related virus is responsible for antibody directed against SV40 in most humans unexposed to known vaccine or monkey sources of SV40 infection.

Candidate cytomegalovirus strain for human vaccination.

Abstract: A strain of human cytomegalovirus called Towne was isolated in WI-38 human fibrolast cell cultures from the urine of an infected infant. It was then passaged 125 times in WI-38, including three clonings, and a pool was prepared in the same cell substrate for use as a potential live attenuated vaccine. The Towne virus has a broad antigenicity and cross-reacts with the AD-169 strain. Several markers of the Towne virus were found which differentiated it from fresh isolates. One of these was resistance of the former to trypsin. The Towne virus was tested for freedom from oncogenicity or other harmful effects in preparation for tests in humans.

A novel murine oncornavirus with dual eco- and xenotropic properties.

Abstract: Infection of Swiss mouse 3T3FL cells with a clonal isolate of Moloney leukemia virus (MLV-IC) resulted in virus progeny composed of at least three different murine helper oncornaviruses. Each entity was purified in appropriate cells by several sequential terminal dilution isolations and was grouwn to high titers. Besides ecotropic MLV-IC there was a pure xenotropic virus and a third novel virus with properties of both eco- and xenotropic viruses. The purified xenotropic virus had a wide host range, was restricted in mouse cells, and was inactivated by normal mouse sera like other xenotropic isolates. The purified virus with hybrid properties (HIX) could infect a wide range of mammalian cells, which included both N and B mouse cells. HIX gave single-hit titrations with equal titers on both mouse and cat indicator cells. Envelope properties of HIX were examined by virus preinfection interference, by interference involving viral glycoprotein, and by neutralization with specific antisera. Both xenotropic and MLV-IC type ecotropic determinants were found on the virus coat. The origins of HIX and the xenotropic virus were investigated in detail. The original MLV-IC stock had HIX type virus in low titer but no detectable pure xenotropic virus. Infection of mouse cells with a single infectious unit of the ecotropic virus from the MLV-IC virus stocks could at times give rise to HIX type virus. HIX type virus, passed once through heterologous rat cells, was subjected to long-term passage either in infected mouse or cat cells. After several months HIX type virus disappeared from some mouse and cat cell systems. The possible hybrid nature of HIX and the origins of newly appearing xenotropic viruses are discussed.

Non-producer human cells induced by murine sarcoma virus.

Abstract: Non-produces (NP) human cells were isolated from transformed foci induced by the Kirsten mouse sarcoma virus. These morphologically altered NP cells produced neither infectious virus nor complement-fixing antigens of the murine sarcoma-leukemia virus complex. However, the sarcoma virus genome could be rescued from these NF cells by co-cultivation with cells carrying "helper" Kirsten mouse leukemia virus or Woolly Monkey leukemia virus. The possible usefulness of these cells in efforts designed to detect covert or repressed RNA tumor viruses in various animal and human tissues is discussed.

Development of a live attenuated varicella vaccine.

Abstract: The Oka strain of varicella virus, isolated in our labolatory, was serially cultivated in guinea-pig embryo cultures (GPEC), and a considerable amount of cell-free virus was obtained from infected cell. GPEC passage virus at the 6th passage level was used in a small scale field trial. Susceptible children of 1 to 10 years old were injected subcutaneously with 100 to 1,000 PFU of virus. No clinical reactions due to the vaccination were observed in any children, and a high rate of antibody response was obtained with viral doses of more than 200 PFU. Attenuated virus obtained by passage in GPEC was propagated in human diploid (WI-38) cells, and it was also effective in inducing an immune response without clinical reactions. The results show that the Oka strain of varicella virus passaged in GPEC and human diploid (WI-38) cells may be used safely and effectively as a live attenuated vaccine.

Host Defenses Against Influenza Virus: The Role of Anti-Hemagglutinin Antibody

Abstract: In CBA mice the protection provided by transferred immune spleen cells or by antibody has been investigated in immunologically intact, cyclophosphamide-treated and thymus-deprived animals infected with A/PR8 virus. The degree of protection was more closely related to serum antibody levels than to the presence of immune lymphocytes in recipients. Comparison of the protective efficiency of various anti-influenza antisera with different specificities within an influenza A subtype indicated that antibodies recognizing the strain-specific determinants of the influenza hemagglutinin have an important role in protection. Physiologic amounts of transferred antibodies were shown to protect immunodepressed mice, suggesting that, provided a sufficient amount of specific antibodies is secreted, the participation of effectors of cell-mediated immunity is not essential. However, our results suggest that thymus-derived lymphocytes have an indirect role in protection by enhancing, through their helper effect, the secretion of anti-influenza antibodies.

Rapid Virus Diagnosis: Application of Immunofluorescence

Abstract: and bone marrow transplantation and a final chapter discusses immunosuppressive therapy in relation to general medical diseases. Immunosuppressive therapy is a field which is only 20 years old and important and major changes occur with great rapidity; it is therefore difficult even with a book of this kind to have kept astride of new events with delays in publication. However, the book has collated the historical aspects, the development of the field and the present ideas on this advancing subject in a comprehensive way. The book is useful for clinicians involved in transplantation, since it integrates the experience of different centres of grafting and describes techniques and difficulties in the individual disciplines. Inevitably, there will be some overlap between chapters on drug usage and side effects but overall each chapter has been written by an author expert in his field and in general each is concise and informative with a balance between established factual data and ongoing experimental work. The book is well presented and introductions and conclusions at the beginning and end of each chapter make it very readable. The bibliography following each chapter is extensive and the index sound. The book is recommended for both general reading and reference, and achieves its aim as an overall review of immunosuppressive therapy in clinical situations.