Search PubMed⌕ Search

Biomedical subjects

J Russell

Publications and source records attributed to J Russell.

At least 91 records · Page 5Linked to original sources
PubMed1999

The reduced adsorption of lysozyme at the phosphorylcholine incorporated polymer/aqueous solution interface studied by spectroscopic ellipsometry.

Coating hydrogel polymers onto solid substrates can reduce the adsorption of proteins onto these surfaces, but the extent of the reduction in protein adsorption is strongly dependent on how the surface layer is coated. We have examined the effect of coating conditions on the structure of thin polymer films formed from a number of poly(methacrylate)-based hydrogel polymers via the dip-coating method. We show in this work how the polarity of the solvent, the speed of lifting, and the annealing temperature affect the thickness and uniformity of ultrathin phosphorylcholine (PC)-incorporated polymer films coated on the surface of native oxide on silicon and the subsequent interaction of these coated surfaces with lysozyme molecules. Our results show that the uniformity of the polymer film, and thus the smoothness of the outer film surface, influence the extent of reduction in protein adsorption. We suggest that the reduction in lysozyme adsorption is the result of a layer of PC groups on the surface of the polymer film. The improvement of the smoothness of the film results in the formation of a close-packed PC layer on the outer surface of the polymer film, leaving few defects or cavities on which protein molecules can bind.

Adsorption↗
PubMed1999

Two intact executive capacities in children with autism: implications for the core executive dysfunctions in the disorder.

Many studies have shown that children with autism perform at a much lower level than control subjects on tests of executive functioning, defined as tasks requiring subjects to hold information in mind while suppressing a prepotent response. These tasks have invariably required subjects to (a) follow arbitrary and novel rules and (b) make a nonverbal response. We report that when one of these features is absent, children with autism are not impaired relative to controls. They perform at a similar level to normally developing children on the "tubes" task (containing no arbitrary and novel rules) and on the day/night task (in which the output is verbal). Results are consistent, at least, with the hypothesis that children with autism are challenged by executive tasks because they are unlikely to encode rules in a verbal form.

Adolescent↗
PubMed1999

Memory for actions in children with autism: self versus other.

In order to ask whether autism is associated with difficulty in self-monitoring we gave a group of children and adolescents with autism a task in which they themselves had to remember whether they or another person had performed certain actions. In our first experiment, three groups of participants had to recall whether placements of picture cards had been made by themselves or by the experimenter. The participants with autism performed at a much lower level than the two comparison groups and, unlike the comparison groups, were not better at recalling their own placements. A second experiment tested the prediction arising from the monitoring-deficit account that the children with autism would be unimpaired when the placement of the items did not alternate between self and other. This prediction was confirmed moderately well. Additionally, in contrast to that of the comparison groups, the performance of the participants with autism was unaffected by whether self or other displaced the items. This is consistent with the existence of a monitoring deficit.

Journal Article↗
PubMed1999

Dissociation, abuse and the eating disorders: evidence from an Australian population.

OBJECTIVE: A number of European and Northern American studies have investigated a possible association between dissociative phenomena, eating disorders, child sexual abuse and self-mutilation. However, there has been little confirmation from other countries and cultures, and the Australian experience of these interrelationships has not previously been studied. METHOD: Dissociative symptomatology and self-reported history of abusive experiences, physical and sexual, were retrospectively studied in a sample of Australian eating disordered patients using a self-report measure, the Dissociation Questionnaire (DIS-Q). RESULTS: As hypothesised, dissociative symptoms were particularly frequent in those who reported child and adult sexual abuse and in those who self-mutilated. A correlation between multiple forms of abuse and higher dissociation scores was only partially upheld. CONCLUSIONS: Interrelationships between victimisation and dissociation are discussed within the context of current knowledge in the field, and brief suggestions for therapeutic strategies are offered.

Adolescent↗
PubMed1999

Role of tumor necrosis factor and interferon gamma in endotoxin-induced E-selectin expression.

Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), potent inflammatory cytokines, are released by macrophages during endotoxin shock. However, the contribution of these cytokines to endotoxin-induced inflammation has not been defined. The expression of E-selectin, measured using the dual radiolabeled monoclonal antibody (mAb) technique, was monitored in different tissues of endotoxin-challenged wild-type and IFN-gamma-deficient mice receiving a mAb to TNF-alpha (TN3). A significant elevation in E-selectin expression occurred in all tissues of wild-type mice challenged with endotoxin. Injection of TN3 in wild-type mice significantly attenuated the endotoxin-induced up-regulation of E-selectin in all tissues (p < .05) except the pancreas. The level of reduction in endotoxin-induced E-selectin expression ranged between 30% in the stomach to 60% in the small intestine. E-selectin expression in endotoxin-challenged, IFN-gamma-deficient mice was significantly reduced in the small and large intestines, when compared with endotoxin-challenged wild-type mice. Although IFN-gamma deficiency had no effect on E-selectin expression in other tissues, administration of TN3 to endotoxin-challenged, IFN-gamma-deficient mice significantly reduced E-selectin expression to levels observed in endotoxin-challenged, wild-type mice that received TN3. These findings indicate that TNF-alpha is essential for achievement of maximal E-selectin expression in most vascular beds during endotoxemia, whereas the contribution of IFN-gamma is largely confined to the small intestine.

Animals↗
PubMed1999

Unique anti-human immunodeficiency virus activities of the nonnucleoside reverse transcriptase inhibitors calanolide A, costatolide, and dihydrocostatolide.

(+)-Calanolide A (NSC 650886) has previously been reported to be a unique and specific nonnucleoside inhibitor of the reverse transcriptase (RT) of human immunodeficiency virus (HIV) type 1 (HIV-1) (M. J. Currens et al., J. Pharmacol. Exp. Ther., 279:645-651, 1996). Two isomers of calanolide A, (-)-calanolide B (NSC 661122; costatolide) and (-)-dihydrocalanolide B (NSC 661123; dihydrocostatolide), possess antiviral properties similar to those of calanolide A. Each of these three compounds possesses the phenotypic properties ascribed to the pharmacologic class of nonnucleoside RT inhibitors (NNRTIs). The calanolide analogs, however, exhibit 10-fold enhanced antiviral activity against drug-resistant viruses that bear the most prevalent NNRTI resistance that is engendered by amino acid change Y181C in the RT. Further enhancement of activity is observed with RTs that possess the Y181C change together with mutations that yield resistance to AZT. In addition, enzymatic inhibition assays have demonstrated that the compounds inhibit RT through a mechanism that affects both the K(m) for dTTP and the V(max), i.e., mixed-type inhibition. In fresh human cells, costatolide and dihydrocostatolide are highly effective inhibitors of low-passage clinical virus strains, including those representative of the various HIV-1 clade strains, syncytium-inducing and non-syncytium-inducing isolates, and T-tropic and monocyte-tropic isolates. Similar to calanolide A, decreased activities of the two isomers were observed against viruses and RTs with amino acid changes at residues L100, K103, T139, and Y188 in the RT, although costatolide exhibited a smaller loss of activity against many of these NNRTI-resistant isolates. Comparison of cross-resistance data obtained with a panel of NNRTI-resistant virus strains suggests that each of the three stereoisomers may interact differently with the RT, despite their high degree of structural similarity. Selection of viruses resistant to each of the three compounds in a variety of cell lines yielded viruses with T139I, L100I, Y188H, or L187F amino acid changes in the RT. Similarly, a variety of resistant virus strains with different amino acid changes were selected in cell culture when the calanolide analogs were used in combination with other active anti-HIV agents, including nucleoside and nonnucleoside RT and protease inhibitors. In assays with combinations of anti-HIV agents, costatolide exhibited synergy with these anti-HIV agents. The calanolide isomers represent a novel and distinct subgroup of the NNRTI family, and these data suggest that a compound of the calanolide A series, such as costatolide, should be evaluated further for therapeutic use in combination with other anti-HIV agents.

Anti-HIV Agents↗
PubMed1999

Quantification of murine endothelial cell adhesion molecules in solid tumors.

Coordinated adhesive interactions between lymphocyte receptors and endothelial cell adhesion molecules (CAMs) are a prerequisite for effector cell entry into tumor stroma. Whereas the diminished leukocyte-endothelial cell interactions observed in tumor microvessels have been attributed to a reduced expression of endothelial CAMs, there is no quantitative data bearing on this issue. The dual-radiolabeled monoclonal antibody technique was used to quantify constitutive and tumor necrosis factor (TNF)-alpha-induced expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), ICAM-2, P-selectin, E-selectin, and platelet-endothelial cell adhesion molecule 1 (PECAM-1) in different vascular beds of normal (C57Bl/6) and RM-1 tumor-bearing mice. When corrected for endothelial surface area, the constitutive expression of selectins in tumor vessels was higher than that observed in other vascular beds. Both constitutive and induced expression of endothelial CAMs in peripheral vascular beds did not differ between normal and tumor-bearing mice. Within the tumor, the magnitude of the upregulation of P-selectin, ICAM-1, and VCAM-1 after TNF-alpha was similar to that within other vascular beds. E-selectin expression in tumors was refractory to TNF-alpha, whereas PECAM-1 and ICAM-2 expression were significantly reduced. Our findings suggest that the presence of a solid tumor does not influence endothelial CAM expression in other vascular beds and that the higher density of selectins in nonstimulated tumor vessels may promote the recruitment of rolling leukocytes in this tissue.

Animals↗
PubMed1999

Detection of de novo hepatitis C virus infection by polymerase chain reaction in hemodialysis patients.

Patients on chronic hemodialysis (HD) treatment have been identified by serological testing, including second- and third-generation enzyme-linked immunosorbent assay (ELISA), as a high-risk group for hepatitis C virus (HCV) infection. Previous studies have shown that de novo cases of HCV may occur in HD units in the absence of other parenteral exposures, which suggests the spread of HCV between patients. In addition, the reverse-transcription polymerase chain reaction (RT-PCR), which directly detects HCV virus, has identified HCV infection in chronic HD patients who are seronegative. The aim of this study was to determine the incidence of HCV infection detected by RT-PCR technology in a large cohort of chronic HD patients. One hundred and twenty chronic HD patients, HCV-negative by serological assays (second-generation ELISA) and molecular techniques (branched DNA and RT-PCR), were observed for a mean period of 9.5 months. They were tested monthly for serum alanine aminotransferase levels (ALT) and by second-generation ELISA. At the end of the follow-up period, they were again evaluated by branched DNA and RT-PCR testing. HCV RNA was detected in patients' sera by RT followed by PCR using two separate primer sets from the 5'-untranslated region of the HCV genome. Southern blot was performed using a digoxigenin-labeled probe. Two patients who had HCV RNA detectable by RT-PCR at the end of the follow-up period remained branched-DNA-negative. Thus, the incidence of de novo acquisition of HCV infection in the current investigation was 2.1% per year. In 1 patient RT-PCR positivity and anti-HCV ELISA seroconversion occurred. The 2nd patient remained anti-HCV ELISA-negative, although viremic. In both patients, the onset of positivity by RT-PCR was associated with a rise of ALT levels into the 'abnormal range' in our laboratory. In these 2 patients, de novo acquisition of HCV infection was observed in the absence of obvious parenteral risk factors other than their presence in the HD environment. In conclusion, de novo acquisition of HCV infection may be undetected by ELISA and branched-DNA assays. The need to monitor chronic HD patients by serial ALT testing is emphasized. RT-PCR should be incorporated into diagnostic testing for HCV infection in chronic HD patients. RT-PCR technology can identify HCV in HD individuals with raised ALT activity.

Alanine Transaminase↗
PubMed1999

Epidemiology and natural history of hepatitis G virus infection in chronic hemodialysis patients.

UNLABELLED: Patients on chronic hemodialysis (HD) have recently been identified as having a high prevalence of hepatitis G virus (HGV) infection. The clinical significance of HGV in this population remains unclear, with no data available as to the acquisition and natural history of HGV infection in this group. AIMS: To assess the prevalence and risk factors of HGV in a large cohort of chronic HD patients, and to evaluate the incidence and clinical consequences of HGV over time in this population. METHODS: Paired sera from 292 patients undergoing chronic HD treatment in four units in the Los Angeles area were tested for HGV RNA before and after they had been on HD for a mean period of 9.7 +/- 1.9 months. HGV was tested by a single-step RT-PCR using two couples of primers located in two different portions (5'UTR, NS5a) of the genome. The amplified products were detected by hybridization with 5' biotin-labeled probes specific for each region. RESULTS: At study entry there were 50 HGV RNA-positive patients, thus the HGV prevalence was 17% (50/292). The multivariate analysis by ordinal logistic regression model showed association (p = 0.0013) between HGV RNA and the location of patients among the HD units. No other significant associations were observed. Three (3/50 = 6%) HGV RNA-positive patients at study entry and 3 (3/41 = 7%) at the end of the follow-up showed a mild increase of alanine aminotransferase (ALT) activity in absence of other apparent causes of liver damage. 35 (70%) out of 50 HGV viremic patients had persistently detectable viremia during the study period; 15 (30%) had non-persistently detectable HGV RNA in the second serum specimen. There was no significant difference between the patients with persistently detectable HGV RNA and those who showed non-persistently detectable HGV viremia with regard to demographic, clinical or virological features. Six patients without detectable HGV viremia at the start of the study showed de novo HGV infection during the follow-up, thus the HGV incidence was 3.07% per year. These individuals did not simultaneously acquire HBV or HCV markers; de novo HGV infection was not associated with other demographic, clinical or virological features. One (16.7%) out of 6 individuals with HGV acquisition had persistently raised ALT levels and chronic HBsAg positivity. The prevalence of HGV was 14% (41/292) at the end of the observation period. CONCLUSIONS: The prevalence of HGV in our HD population was high; HGV positivity was strongly associated with the location of HD patients among the units; some HD individuals with current HGV infection showed biochemical signs of liver disease without other apparent causes. De novo acquisition of HGV occurred within HD units in the absence of evident parenteral risk factors for HGV other than their presence in the HD environment. A large portion of HGV viremic patients showed non-persistently detectable HGV viremia during the study. Acquisition of HGV was not associated with a rise in ALT activity unlike prior experience with de novo HCV in HD patients. Further investigations are warranted to explain the modes of HGV acquisition and the clinical significance of HGV in th HD population.

Chronic Disease↗
PubMed1999

A successful strategy. Garnering community support for contraceptives services to be provided in a school-based health center.

The original planning group for a school-based health center sensed controversy in the community over the provision of contraceptive services at the high school. They initially made the decision to exclude contraceptive services; however, the planning group provided a stipulation in their package that an assessment of the community regarding contraceptive services be conducted after the clinic had been open for one year. This article describes the strategies and activities of the clinic staff at the one-year point to assess community values and support comprehensive services to adolescent students. We began with fact gathering, then planned a parent survey and faculty survey, followed by faculty focus groups, meetings with clergy and a second survey that included all parents in the school, as well as parents of incoming students. Community forums were held to obtain feedback and provide information. Our efforts culminated in a school board vote of six to one to allow us to provide contraceptive services.

Adolescent↗
PubMed1999

Turning a negative into a positive: vitamin D receptor interactions with the avian parathyroid hormone response element.

1 ,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] negatively regulates expression of the avian PTH (aPTH) gene transcript, and a vitamin D response element (VDRE) near the promoter of the aPTH gene had previously been identified. The present report assessed whether the negative activity imparted by the aPTH VDRE could be converted to a positive transcriptional response through selective mutations introduced into the element. The tested sequences were derived from individual and combined mutations to 2 bp in the 3'-half of the direct repeat element, GGGTCAggaGGGTGT. Cold competition experiments using mutant and wild-type oligonucleotides in the mobility shift assay revealed minor differences in the ability of any of these sequences to compete for binding to a heterodimer complex comprised of recombinant proteins. Ethylation interference footprint analysis for each of the mutants produced unique patterns over the 3'-half-sites that were distinct from the weak, wild-type footprint. Transcriptional outcomes evaluated from a chloramphenicol acetyltransferase reporter construct utilizing the aPTH promoter found that the individual T-->A mutant produced an attenuated negative transcriptional response while the G-->C mutant resulted in a reproducibly weak positive transcriptional outcome. The double mutant, however, yielded a 4-fold increase in transcription, similar to the 7-fold increase observed from an analogous construct using the human osteocalcin VDRE. UV light crosslinking to gapped oligonucleotides assessed the polarity of heterodimer binding to the wild-type and double mutant sequences and was consistent with the vitamin D receptor preferentially binding to the 5'-half of both elements. Finally, DNA affinity chromatography was used to immobilize heterodimer complexes bound to the wild-type and double mutant sequences as bait to identify proteins that may preferentially interact with these DNA-bound heterodimers. This analysis revealed the presence of a p160 protein that specifically interacted with the heterodimer bound to the wild-type VDRE, but was absent from complexes bound to response elements associated with positive transcriptional activity. Thus, the sequence of the individual VDRE appears to play an active role in dictating transcriptional responses that may be mediated by altering the ability of a vitamin D receptor heterodimer to interact with accessory factor proteins.

Animals↗
PubMed1999

Vitamin D receptor interactions with the rat parathyroid hormone gene: synergistic effects between two negative vitamin D response elements.

Vitamin D response elements (VDREs) that are required for negative regulation of rat parathyroid hormone (rPTH) gene expression have been characterized. Gel mobility shift assays using DNA restriction enzyme fragments and recombinant proteins for vitamin D and retinoic acid X receptors (VDR/RXR) revealed a sequence between -793 and -779 that bound a VDR/RXR heterodimer with high affinity (VDRE1). Furthermore, a lower affinity site (VDRE2) was detected that acted in combination with VDRE1 to bind a second VDR/RXR complex. As determined by ethylation interference analysis, the nucleotide sequence of VDRE1 consisted of GGTTCA GTG AGGTAC, which is remarkably similar to the sequence of the negative VDRE found in the chicken PTH (cPTH) gene. Using the same technique, VDRE2 was identified between positions -760 and -746 and contained the sequence AGGCTA GCC AGTTCA. Functional analysis was determined by transfection studies with plasmid constructs that expressed the gene for chloramphenicol acetyl transferase (CAT). The ability of the VDREs to regulate gene expression was tested in their native context with the rPTH promoter as well as when positioned immediately upstream from the cPTH promoter. With either plasmid construct, exposure to 10(-8)M 1,25(OH)2D3 resulted in a 60-70% decrease in CAT gene expression when both VDRE1 and VDRE2 were present. Examination of the individual VDREs showed that inhibition by 10(-8) M 1,25(OH)2D3 was only 35-40% when just VDRE1 was present. By itself, VDRE2 was even less effective, as significant inhibition of CAT activity (20%) was observed only in the presence of higher concentrations of 1, 25(OH)2D3 (10(-7)M) or when a plasmid vector that overexpressed the VDR protein was cotransfected. In conclusion, the rPTH gene contains two negative VDREs that act in concert to bind two RXR/VDR heterodimer complexes and that both VDREs are required for maximal inhibition by 1,25(OH)2D3.

Animals↗
PubMed1999

Ultracentrifugation and concentration of a large volume of serum for HCV RNA during treatment may predict sustained and relapse response in chronic HCV infection.

The ability to predict accurately a sustained response during therapy in patients with hepatitis C virus (HCV) infection is unavailable. The aim of this study was to differentiate, during therapy, patients who would relapse from those with a sustained response by ultracentrifugation for residual serum HCV RNA. Sixty-one specimens (from 32 patients) collected during interferon therapy were assessed by ultracentrifugation. All were negative using a quantitative polymerase chain reaction (PCR) (detection limit < or = 100 copies/ml). One-milliliter aliquots were ultracentrifuged at 23,000 x g (160 min), and then the nucleic acid pellet was extracted, precipitated, and resuspended. Qualitative PCR was carried out in quadruplicate using two separate 5'UTR primer sets (8 results/specimen). A specimen was positive if > or = 1 gels was positive compared to controls. At weeks 12 and 24, 9/9 (100%) sustained response patients were negative by ultracentrifugation. In the 23 relapse patients at week 12, 7/12 specimens were positive; at week 24, 7/14 were positive. Earlier time points could not differentiate the patients' eventual response to therapy. The predictive value of a positive ultracentrifugation test for relapse at week 12 or 24 was 100%. The predictive value of a negative test for sustained response was 62% and 50% at week 12 and 24, respectively. These preliminary results indicate that patients with an eventual sustained response will have no detectable serum HCV RNA by week 12 or week 24. A positive result is 100% predictive of relapse.

Adult↗
PubMed1999

What do executive factors contribute to the failure on false belief tasks by children with autism?

As children with autism have pervasive executive difficulties it is necessary to determine whether these contribute to their often-reported failure on the false belief task. Failure on this task is frequently taken to diagnose the lack of a "theory of mind". We report two studies using two tasks that make similar executive demands to the false belief task. The first experiment showed that children with autism are significantly challenged by a "conflicting desire" task, which suggests that their difficulty with the false belief task is not rooted in difficulty with grasping the representational nature of belief. In the second study children with autism were also found to be impaired on a novel version of the "false photograph task". A parsimonious reading of these data is that their difficulty with all three tasks is due to commonalities in the tasks' executive structure.

Autistic Disorder↗
PubMed1999

Increased expression of mutated Ha-ras during premalignant progression in SENCAR mouse skin.

The ras proto-oncogene family products are membrane-associated, guanine nucleotide-binding proteins that serve as a molecular switch for signal transduction pathways in a diverse array of organisms. In the mouse skin two-stage carcinogenesis model, a specific point mutation in Ha-ras codon 61 is responsible for the initiation event. Here we investigated whether Ha-ras protein and mRNA expression change during premalignant progression. Also, we assessed the Ha-ras mutated allele after these changes. To those ends, we analysed the Ha-ras expression profiles in normal and hyperplastic skin, papillomas, and squamous cell carcinomas by western blotting, reverse transcription-polymerase chain reaction, and in situ hybridization. Increased levels of Ha-ras expression were observed at specific times during promotion. These changes were followed by an increase in the level of expression of the Ha-ras mutated allele. These results suggest that increased expression of Ha-ras mutated alleles may have an important role during premalignant progression.

Alleles↗
PubMed1999

A comparison of noncontrast computerized tomography with excretory urography in the assessment of acute flank pain.

PURPOSE: We compare noncontrast enhanced computerized tomography (CT) and excretory urography (IVP) in the evaluation of acute flank pain. MATERIALS AND METHODS: A total of 40 consecutive patients presenting to the emergency department with acute flank pain were evaluated with noncontrast CT, films of the kidneys, ureters and bladder, and IVP. The patients were treated according to the clinical picture. All 40 sets of evaluations were later assessed randomly by an independent consultant radiologist for the presence, size and location of a stone, ureteral dilatation and secondary signs of ureteral obstruction. RESULTS: Of 40 patients 12 had no calculus and 28 had a calculus confirmed on removal or documented passage of a stone. Absence of a stone was based on clinical and radiological followup with clinical resolution. CT revealed all 28 calculi and no calculus in 11 of 12 patients with 100% sensitivity and 92% specificity. IVP demonstrated 18 calculi (64% sensitivity) and no calculus in 11 of 12 patients (92% specificity). Ureteral obstruction was seen in 28 of the 40 patients, and CT and IVP were equivalent in detection (100% sensitivity). Films of the kidneys, ureters and bladder alone demonstrated 15 of 28 stones (54% sensitivity). CONCLUSIONS: Noncontrast CT is an accurate, safe, rapid technique to assess acute flank pain, and the evaluation of choice for patients who would otherwise require IVP for diagnosis.

Acute Disease↗
PubMed1998

The RET/PTC3 oncogene: metastatic solid-type papillary carcinomas in murine thyroids.

Our research goal is to better understand the mechanisms controlling the initiation and progression of thyroid diseases. One such disease, papillary thyroid carcinoma (PTC), is the leading endocrine malignancy in the United States. Recently, a family of related fusion proteins, RET/PTC1-5, has been implicated in the early stages of PTC. Although all five members of this family have the c-RET proto-oncogene kinase domain in their COOH terminus, little is known about how these genes alter follicular cell biology. Consequently, to answer questions related to the mechanism of the RET/PTC fusion protein action, we have devised a molecular genetic strategy to study PTC using a mouse model of thyroid disease. A new member of this fusion oncogene family, RET/PTC3, which has been implicated in more cases of solid tumor carcinoma (79%) than PTC1 or PTC2 and predominates (80%) in radiation-induced thyroid cancer of children, was investigated in our study. We have generated transgenic mice expressing human RET/PTC3 exclusively in the thyroid. These mice develop thyroid hyperplasia, solid tumor variants of papillary carcinoma and metastatic cancer. This new transgenic line will be useful in deciphering the molecular and biological mechanisms that cause PTC and histological variations in humans.

Animals↗