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PubMed1983

Follicular growth and kinetics during the estrous cycle, pregnancy and postpartum in the Indian mole rat (Bandicota bengalensis).

Follicular growth and kinetics were studied in detail in the ovaries of the Indian mole rat (Bandicota bengalensis) during various stages of the estrous cycle; days 7, 12, 15, 19, and 21 of pregnancy; and day 2 postpartum. The sizes of follicles, oocytes, nuclei, and nucleoli were measured. In all rats, regression coefficients, a, and intercepts, b, were calculated in oocyte/follicle, oocyte nucleus/follicle and oocyte nucleus/oocyte regressions. The oocyte reached its maximum size when the average follicle diameter was 117 microns in nonpregnant rats and 131 microns in pregnant rats. The oocyte nucleus attained maximum size when the follicle diameter was 110 microns during the estrous cycle and 111 microns during pregnancy and postpartum. Maximum values of the diameter of the largest antral follicle and average diameter of the four largest antral follicles were observed during proestrus (473 and 442 microns, respectively) and on day 21 of pregnancy (611 and 538 microns, respectively). Chi 2 analysis showed that distribution of various types of follicles was not independent of the stage of the estrous cycle and pregnancy. In estrus and metestrus most of the follicles were between stages I and V. However, by diestrus and proestrus, follicles of all size groups developed. The numbers of stage I and II follicles did not differ as pregnancy advanced. More stage V follicles were present on day 12 than on day 7 of pregnancy; however, their numbers decreased by day 15. Afterwards, progressive increase of stage V and (VI + VII) follicles was observed until day 21. This was accompanied by the shift of follicles from stage (III + IV) on days 19 and 21 of pregnancy and even of stage II on day 2 postpartum. Wherever possible, the results have been compared with previous observations in various rodent species.

Animals↗

PubMed1992

Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus population.

The composition of human immunodeficiency virus type 1 (HIV-1) clonal populations at different stages of infection and in different compartments was analyzed. Biological HIV-1 clones were obtained by primary isolation from patient peripheral blood mononuclear cells under limiting dilution conditions, with either blood donor peripheral blood lymphocytes or monocyte-derived macrophages (MDM) as target cells, and the biological phenotype of the clones was analyzed. In asymptomatic individuals, low frequencies of HIV-1 clones were observed. These clones were non-syncytium inducing and preferentially monocytotropic. In individuals progressing to disease, a 100-fold increase in frequencies of productively HIV-1-infected cells was observed as a result of a selective expansion of nonmonocytotropic clones. In a person progressing to AIDS within 19 months after infection, only syncytium-inducing clones were detected, shifting from MDM-tropic to non-MDM-tropic over time. From his virus donor, a patient with wasting syndrome, only syncytium-inducing clones, mostly non-MDM-tropic, were recovered. Parallel clonal analysis of HIV-1 populations in cells present in bronchoalveolar lavage fluid and peripheral blood from an AIDS patient revealed a qualitatively and quantitatively more monocytotropic virus population in the lung compartment than in peripheral blood at the same time point. These findings indicate that monocytotropic HIV-1 clones, probably generated in the tissues, are responsible for the persistence of HIV-1 infection and that progression of HIV-1 infection is associated with a selective increase of T-cell-tropic, nonmonocytotropic HIV-1 variants in peripheral blood.

Acquired Immunodeficiency Syndrome↗

PubMed1992

[Late results following implantation of aortic bifurcation prosthesis].

From January 1976 to December 1986 181 patients with chronic arterial occlusive disease were provided with an Y-prosthesis of the aorta. In a retrospective study we reviewed the history of these patients. From 130 (72%) patients we obtained information about the further course of the disease, 83 (46%) patients were reexamined. Depending on the preoperative stage (Fontaine-Ratschow classification) of the chronic arterial occlusive disease, patients in higher stages had a greater benefit from the implantation by shifting into a more satisfactory stage. The majority of patients without any postoperative complaints (48%) belonged to the group, preoperatively classified into stage II B. Depending on the type of occlusion the best results were obtained in unique occlusions of the aorto-iliac vascular segment. 50% of the reexamined patients had no complaints although in 61% of these cases the superficial femoral artery was occluded in the mean time. 47 patients deceased during the interval of observation. In most cases death was caused by other manifestations of the basic disease (e.g. cardiac infarction or cerebral apoplexy). The 10-year-survival rate was 59%. The majority of patients with chronic occlusive disease of the pelvic arteries profited from the implantation of an aortal Y-prosthesis. The long-term success of this operation with its low lethality depends on the preoperative stage and the extent of the occlusive process.

Aorta, Abdominal↗

PubMed2000

The impact of prestimulus EEG frequency on auditory evoked potentials during sleep onset.

Auditory evoked potentials were recorded during wakefulness, Stage 1, and Stage 2 non-REM sleep using a three-tone auditory oddball paradigm. Stage 1 sleep was divided into trials preceded by alpha and those preceded by theta. A negative wave peaking at about 100 ms, N1, displayed a significant decrease in amplitude with the onset of Stage 2 sleep. A later N2 peaked at about 250 ms in the waking state. This changed into a sleep-specific negative wave peaking at 300 ms (N300) at the alpha-theta transition within Stage 1. The P300 displayed a similar shift to become a P450 in Stage 2 sleep. N550 was specific to Stage 2, and was larger in response to rare, rather than frequent stimuli. There was no evidence of any enhancement to relevant rare stimuli compared with irrelevant rare stimuli.

Adult↗

PubMedDate not supplied

[Videofluoroscopic evaluation of the functional significance of the epiglottis in adults].

Our intention was to define the functional role of the epiglottis. Accordingly, we analysed its movements and correlation in 53 videofluroscopic exams: 26 were good health volunteers, 25 were patients with dysphagia and two were persons with pharyngeal diverticula. The exams register the rest phase, chewing, and the swallowing movements during the intake of the saliva, water, barium solution and different volumes of mass made with crumbled bread mixed with barium powder. We can see three sequential stages in epiglottic movement during swallowing. The first stage involves an upward epiglottic shift determined by hioepiglottic ligament, associated with a simultaneous bending caused by the tongue backward projection. The second stage is a posterior rotation of the epiglottis, limited by the adjustment of the epiglottic tubercle to the vestibular fold, determined by laryngeal upward shift against hyoid bone. The third stage in which occurs an eversion of the free extremity of the epiglottis beyond the horizontal plane can be absent in slow pressure swallowing. All stages of the epiglottic dynamics are passive. We have shown that the epiglottis has a protective action on the repiratory airways not limited to swallowing. It participates, during swallowing and regurgitation (vomica), through the passive adjustment of the intralaryngeal posterior surface of the epiglottis (epiglottic tubercle) to the vestibular folds. Both before and after swallowing, when frequently there are escapes of residues and small volumes out of the oral cavity, the epiglottis protects the repiratory airways, through its participation in the formation of the valleculae and as an insertion point for the aryepiglottic folds. In association with epiglottis participation there is a stretching of the aryepiglottic folds that allow a definition of the lateral channels. The upward and forward movements of the larynx associated with the opening of the pharyngoesophageal transition, that occurs synchronously with the ejection of the swallowed bolus, has been shown to be an important factor in the protective laringeal mechanism. The increase in the laryngeal resistance, in which the epiglottis takes part, is only efficient when there is wide and synchronous opening of the pharyngoesophageal transition. In this context the epiglottis is a secondary element in the protection of the respiratory airways.

Adolescent↗

PubMed1975

Studies on the induction of mitotic gene conversion by ultraviolet irradiation. II. Action spectra.

Action spectra for the induction of intragenic mitotic recombination (gene conversion) at the trp 5 locus by UV are presented for three cell stages (T0, T9 and T16) taken from synchronously growing cultures of Saccharomyces cerevisiae. The spectra over the range from 230 to 300 nm were taken mostly in 5-nm steps. The peak of action spectra was significantly shifted, regardless of the stage, toward the longer wavelengths as compared with that of the absorption spectrum of DNA (258 nm) or even that of thymine (265 nm). In one extreme case (T16), the peak was shifted 17 nm from the absorption peak of DNA. Further, the spectrum changed its shape as the cell stage advanced from non-dividing (unbudded) (T0) to a dividing phase (T16). Furthermore, the induction cross section decreased by a large factor (about 40), regardless of the wavelength, in going from T0 to T16. From observations of the high photoreversibility of induced conversions, the major primary damage was thought to be pyrimidine dimers in the DNA. One plausible explanation, though not quite satisfactory from the quantitative viewpoint for these findings was that the increasing RNA during growth would screen the incident UV differentially with respect to the stage. If this explanation is correct, thymine dimers may still be considered, in spite of the shifts and deformations in the action spectra, as the major primary damage that triggers the long series of processes leading to gene conversion. Conventional methods for obtaining action spectra are discussed in comparison with the present method, which was based on sensitivity parameter a in the proposed dose (t)-frequency (f) relation, f = (at)alpha (alpha is the multiplicity parameter).

DNA↗

PubMed1996

Three stages of medical dialogue.

The negative consequences of physicians' failure to establish and maintain personal relationships with patients are at the heart of the "humanistic crisis" in medicine. To resolve this crisis, a new model of doctor-patient interaction is proposed, based on the ideas of Martin Buber's philosophy of dialogue. This model shows how the physician may successfully combine the personal (I-Thou) and impersonal (I-It) aspects of medicine in three stages. These "Three Stages of Medical Dialogue" include: 1. An Initial Personal Meeting stage, which initiates the doctor-patient relationship and involves mutual confirmation; 2. An Examination stage, which requires a shift from a personal to an impersonal style of interaction; 3. An Integration Through Dialogue or "Healing Through Meeting" Stage, which involves the integration of the impersonal medical data into the ongoing dialogue between doctor and patient, as a basis for shared decision-making. The use of the model, as well as common failures of doctor-patient dialogue are discussed.

Aged↗

PubMed2003

Growth and morphogenesis at the vegetative shoot apex of Anagallis arvensis L.

A non-destructive replica method and a 3-D reconstruction algorithm are used to analyse the geometry and expansion of the shoot apex surface. Surface expansion in the central zone of the apex is slow and nearly isotropic while surface expansion in the peripheral zone is more intense and more anisotropic. Within the peripheral zone, the expansion rate, expansion anisotropy, and the direction of maximal expansion vary according to the age of adjacent leaf primordia. For each plastochron, this pattern of expansion is rotated around the apex by the Fibonacci angle. Early leaf primordium development is divided into four stages: bulging, lateral expansion, separation, and bending. These stages differ in their geometry and expansion pattern. At the bulging stage, the site of primordium initiation shows an intensified expansion that is nearly isotropic. The following stages develop sharp meridional gradients of expansion rates and anisotropy. The adaxial primordium boundary inferred from the surface curvature is shifting until the separation stage, when a crease develops between the primordium and the apex dome. The cells forming the crease, i.e. the future leaf axil, expand along the axil and contract across it. Thus they are arrested in this unique position.

Algorithms↗

PubMed1987

Proliferation of human testicular tumours.

Whole tumour perfusion with radioactive DNA precursors reveals that proliferation of human testicular tumours differs widely depending on type and stage of development. In seminomas a homogeneous distribution of proliferating cells at early stages is followed by a shift of the growth fraction to the periphery at advanced stage. Embryonal carcinomas show a chessboard-like pattern of proliferating fractions with high 3H-thymidine labelling indices and short tpot. In mature teratomas proliferation is low. It increases in immature teratocarcinomas. Lack of proliferation is observed in beta-hCG-positive syncytiotrophoblastic cells of choriocarcinomas, the growth fraction being limited to the cytotrophoblastic compartment.

Adult↗

PubMed1999

Ten-year survey of lung cancer treatment and survival in hospitals in the United States: a national cancer data base report.

BACKGROUND: Primary lung cancer accounts for approximately 14% of all new cancers and 28% of cancer deaths in the U.S. Previous reviews have shown limited progress in the management or outcome of this devastating disease. METHODS: Reports described in the current study were 713,043 primary lung malignancies diagnosed between 1985 and 1995 and submitted to the National Cancer Data Base. Demographic, tumor, and treatment patterns for 1995 were compared with those for 1985-1987, 1988-1991, and 1992-1994. Ten-year relative survival rates were presented for selected demographic and histologic groups and 5-year relative survival rates were presented by stage and dominant treatment modalities for major carcinoma histologies. RESULTS: Previously observed demographic trends were evident, with increasing proportions of patients being older, female, and African American, and more cases reported to be adenocarcinomas. There was a substantial shift toward more complete staging but no change in the distribution of staged cases. Compared with earlier patients, fewer 1995 patients received cancer-directed treatment. More surgical patients underwent lymph node dissection, and radiation treatment was supplemented more often with chemotherapy. The overall 10-year relative survival rate was 7%. The 5-year survival for American Joint Committee on Cancer Stage I surgical patients was >50% for all nonsmall cell histologic groups. CONCLUSIONS: Recent shifts in treatment, although minimal, are consistent with current literature concerning the effectiveness of lung carcinoma treatment. The authors believe that the overall poor survival of lung carcinoma patients points to a continuing need for improved prevention and treatment measures. The comparatively superior survival of Stage I nonsmall cell lung carcinoma surgical patients indicates that a substantial number of patients have the potential to be treated successfully.

Adult↗

PubMed1997

Correlation among thermosensitive period, estradiol response, and gonad differentiation in the sea turtle Lepidochelys olivacea.

Reptile embryos with temperature sex determination have a thermosensitive period (TSP). The finding that exogenous estradiol (E2) overcomes the effect of male-promoting temperature led to the idea that temperature may regulate estrogen concentration in the gonad during TSP. Since interspecific variations in TSP and in the effect of exogenous E2 exist, we undertook a study in the olive ridley Lepidochelys olivacea. Four parameters were correlated: the TSP (time dimension), the thermosensitive stages (rate of development), gonad development (histological aspect), and the estradiol response. Two kinds of experiments were performed: (1) Eggs were shifted once, at different stages of development, from a male-promoting temperature to a female-temperature (or vice versa) for the remainder of development. (2) Eggs at male-promoting temperature were treated once with 6 or 12 microg of estradiol (E2) at various times of incubation. Sex ratio was established around hatching in each experimental series. We found that the temporal dimension of the TSP was around 7 days (Days 20-27 of incubation) at a male-promoting or a female-promoting temperature. The rate of development of the whole embryo and gonadal growth was faster at female-promoting temperature than at male-promoting temperature. Formation of the genital ridge began at stage 21-22 and histological differentiation of the gonads occurred around stage 26-27. Although these stages coincided with the TSP, at male-promoting temperature the thermosensitive stages occurred earlier (from stages 20-21 to stages 23-24) than at female-promoting temperature (from stages 23-24 to stages 26-27). Thus, at male promoting-temperature, sex was determined in embryos with incipient or undifferentiated gonads. In contrast, E2 treatment continued to feminize the gonads of embryos at a male-promoting temperature beyond the TSP up to stage 25-26, but the E2-induced ovaries were significantly smaller than temperature-induced ovaries. It is suggested that the doses of E2 used were higher than the concentration of endogenous E2 required for normal sex determination. The lack of correlation between sex determination and gonad differentiation suggests that irreversible molecular processes underlying sex determination occur earlier at male- than at female-promoting temperature. Results suggest that the male sex may be the default state and that the female condition must be imposed upon it.

Animals↗

PubMed2002

Incidence and tumour stages of breast cancer in the region of Aachen, Germany.

We present epidemiological data of female breast cancer in the region of Aachen (Germany) including incidence and tumour stages for the period 1996-1997. Furthermore, we compare epidemiological data from Aachen with data from the directly neighbouring Dutch region South-Middle Limburg before and after the introduction of a national mammographic screening programme. The field study of breast cancer was undertaken at the Institute of Pathology and Comprehensive Cancer Center at the University of Aachen, supported by the Federal Ministry of Health (Germany), using data files from the Cancer Registry Aachen. The patient's consent to collect all data concerning her epidemiological and social situation as well as information on the outcome of disease was obtained in 83.4% of all cases. The remaining 16.6% of the cases without a patient's consent are based on histopathological reports. Only those patients are included who were documented as residing in the region of Aachen at the time of diagnosis. Tumour cases were counted according to International Agency for Research on Cancer rules and tumour stages are classified according to UICC guidelines. Incidence rates are calculated as crude value, adapted to the European and World Standard population (ESR, WSR), and the age specific incidence is presented in 5-year intervals. The cumulative risk is assessed for a certain life span by summarizing the age-specific incidences. The age-standardized breast cancer incidence rate in Aachen was 94 per 100 000 women in 1996 and 90 cases of invasive breast cancer per 100 000 women in 1997 according to the ESR. The cumulative risk of developing breast cancer in the life span ranging from 0 to 74 years is approximately 8%. The stage distribution of breast cancer reveals only 4% favourable carcinomata in situ, but 12% advanced T4 tumours. T1 and T2 tumour stages count for about 40% and T3 tumour stages about 4%. Incidence rates and the tumour stages of breast cancer in the region of Aachen during 1996 and 1997 are similar to the data obtained from the directly neighbouring Cancer Center of the region South-Middle Limburg, in the Netherlands, in 1989/1990 before the beginning of the national breast cancer screening programme. However, major differences are found in terms of the incidence and the tumour stages between Aachen 1996/1997 and South-Middle Limburg 1995/1996 after the introduction of the mammographic screening. The incidence of female breast cancer in Aachen, Germany, was high and in the range of the data from other cancer registries in Europe without national screening programmes. The tumour stages at diagnosis in Aachen were not very favourable, especially in elderly women. An increase of the cancer incidence and a shift of the tumour stages to more favourable ones were observed in the neighbouring Dutch region of South-Middle Limburg, comparing data from 1989/90 and 1995/96. This is probably as a result of the national mammographic screening programme. As data from Aachen were similar to Limburg's data from 1989/90 before the mammographic screening was introduced, it will be important to follow and compare the cancer incidence and the tumour stages in the future.

Breast Neoplasms↗

PubMed1989

[The effect of mass chest x-ray on early detection of bronchial cancer].

On 30.6.1983, mass radiographic screening was abandoned despite objections to the effect that it offered the only chance of detecting carcinoma of the lung at an early stage. In a retrospective analysis of our patient material comprising 1.010 patients with bronchial carcinomas seen within the period between 1.1.1980 to 31.12.1986, we investigated the question as to whether these objections might not be justified. Four hundred and thirty-seven patients seen prior to 30.6.1983 were compared with 537 patients examined after this date, on the basis of the following parameters: age - sex - symptomatology - cancer stage - histology - treatment. After stopping mass radiographic screening, an increase in age and symptomatic tumour findings was observed, and thus a shift towards more advanced stages of carcinoma. A relative decrease in the number of squamous cell carcinomas, and a relative increase in the number of adenocarcinomas were observed. All the parameters in the patients identified at mass radiographic screening were comparable with those seen in patients identified incidentally. In comparison with symptomatic patients, those identified by mass radiography screening more frequently presented with earlier tumour stages, and the lesions were more frequently resectable. All in all, over a period of three and one-half years, mass radiographic screening revealed 23.8% of all cancers of the lung, and 36.8% of all resectable lesions. After the abandonment of mass radiographic screening, an increase in more advanced and symptomatic tumours was observed.

Carcinoma, Bronchogenic↗

PubMedDate not supplied

Distribution of p53 codon 72 polymorphisms in ovarian tumour patients and their prognostic significance in ovarian cancer patients.

BACKGROUND: The p53 gene is frequently mutated in various human tumours. In addition, single nucleotide polymorphisms are often observed in exons and introns of the p53 gene in normal tissues and tumours. MATERIALS AND METHODS: The prevalence of a polymorphism involving codon 72 of exon 4 in the p53 gene was studied in peripheral white blood cells and tumour tissues from Danish ovarian tumour patients and in peripheral white blood cells from controls. The analyses were performed by Polymerase Chain Reaction (PCR), Restriction Fragment Length Polymorphism (RFLP) and DNA sequencing. The amino acid residue at this position is either arginine (p53-Arg) or proline (p53-Pro). RESULTS: There was no correlation between the frequency of the three genotypes (Pro/Pro, Arg/Arg and Arg/Pro) and age, stage or histological type of the tumour. A significant difference in survival was observed between ovarian cancer stage III patients with a shift from one genotype in the blood to another genotype in the tissue and patients with no shift (p=0.0216). CONCLUSION: Kaplan-Meier survival analyses and multivariate Cox regression analysis stratified to stage III ovarian cancer patients showed that a shift from one genotype in the blood to another genotype in the tissue is a prognostic factor in Danish ovarian cancer patients.

Adult↗

PubMed2026

Integrative multi-omics analysis reveals lipid/metabolite dysregulation and temporal decoupling in disease progression.

Our study presents and applies a metabolomics-driven multi-omics integration strategy to elucidate dynamic pathway interactions during disease progression. We analyzed longitudinal metabolomics datasets from a Duchenne muscular dystrophy (DMD) mouse model (6-30 weeks) and an acute Bothrops asper envenomation model (1-24 h) to contrast chronic versus acute inflammation. In the DMD model, we predicted phased cross-talk between sphingolipid metabolism and neurotrophin signaling: an early proteomic surge followed by lipid-mediated amplification and a late convergence at the protein level. Arginine and proline metabolism exhibited early metabolite accumulation preceding delayed inferred protein changes, consistent with impaired nitric oxide synthesis and argininemia-like effect. We also predicted late-stage activation of the AGE-RAGE pathway in DMD, likely triggered by ceramide buildup, and an autophagy-related lipid metabolic shift at mid-stage. In the envenomation model, tryptophan-kynurenine and nicotinamide pathways for NAD⁺ biosynthesis were rapidly perturbed at the metabolite level (1-3 h) but induced corresponding predicted enzymes only by 24 h. Thyroid hormone signaling showed an early coupling of substrate availability (tyrosine surge at 1 h) with predicted stress-response proteins and a second, delayed wave of inferred transcriptional regulators at 24 h. Acute envenomation also triggered immediate glycine/serine utilization possibly for antioxidant defense and glycerophospholipid breakdown (via phospholipase A₂), whereas chronic DMD showed sustained glycine/serine engagement and inferred, unresolved phospholipid perturbation without protein-level compensation, which may result from chronic oxidative stress. Overall, our integrative analysis revealed time-specific, multi-layer molecular perturbations distinguishing acute toxin injury from chronic muscle degeneration. Key metabolic control points (ceramide accumulation, arginine flux diversion, autophagy-lipid cross-talk, NAD⁺ salvage timing) were identified, highlighting potential targets for stage-specific therapeutic or nutritional interventions.

Animals↗

PubMed1990

[The importance of analysis and regulation of the activities at the current stage of development of public health].

The shifting of emphasis from a branch to territorial planning at the stage of restructuring public health generates the necessity to develop local labour standards, and conditions the needs of public health administrators in methodological provision of this work. The article defines a wide range of tasks for the setting of labour standards which are being solved at the centralized level and at health institutions; main conditions are laid down which are to be followed while working out local standards.

Administrative Personnel↗

PubMed1976

Improved survival in hodgkin's disease.

All patients below the age of 66 whose Hodgkin's disease was treated at the Massachusetts General Hospital between July 1, 1965 and June 30, 1973 were analyzed. The patients were divided into an early group seen before November 1, 1968 and a later group seen after that date. Survival and survival without recurrence were calculated by the actuarial method of Berkson and Gage, and compared with figures obtained from a historical series seen at this institution between 1948 and 1964. In the most recent period (1969-1973), 87% of patients with all stages of Hodgkin's disease were alive five years after diagnosis, a remarkable improvement over the 65% survival of the 1965-1968 group and the 34% survival of the historical series. The excellent survival of the recent group was a result of improved management of patients with advanced disease (Stages III and IV), most plausibly attributed to better appreciation of the extent of disease by surgical staging and to the shift from total nodal irradiation to combination chemotherapy for initial treatment of these patients. Recurrence after irradiation was extremely uncommon in patients in Stage IA and IIA (lymphangiogram-negative, asymptomatic) subjected to aging laparotomy, while similarly staged and irradiated patients in Stages IB and IIB (lymphangiogram-negative, symptomatic) did much less well. Except for the surgically staged patients in Stages IA and IIA, the continuing high relapse rate indicates that five-year survival, even when relapse-free, is not synonymous with cure, and emphasizes the need for caution in predicting the ultimate cure rate with current therapy.

Antineoplastic Agents↗

PubMed1984

Sequential expansion of antibody heterogeneity during the response to bacterial alpha-amylase.

By analyzing antibody heterogeneity during the primary immune response to bacterial a-amylase (B alpha A) in high-responder F1 hybrid mice between C57BL/6 (B6) and C3H/He (C3) mice with the use of isoelectric focusing (IEF), it was shown that the maturation of the primary IgG antibody response consisted of at least two stages. The response of every mouse tested was initiated with the production of specific antibody focused as a limited set of bands in a narrow pH range, and the subsequent rise in antibody titer was associated with the sequential expansion of the spectra involving the appearance of new bands in the pH gradient adjacent to the initial bands. A further rise was accompanied only by intensified staining of the pre-existing bands. These two stages were distinguishable regardless of the antigen dose, although increasing the dose led to widely distributed spectra of focused antibodies and an early shift from the first stage to the second. The sequential expansion of spectra following the appearance of initial antibodies with limited isoelectric point (pI) values was not unique to the anti-BaA antibody response, because similar results were obtained with the antibody response to an immunologically unrelated antigen, Taka-amylase A (TAA). Thus, the appearance of initial antibodies in a limited pH range, overlapping among all F1 hybrids tested, is not a direct reflection of similarity in the determinant specificities of these antibodies among different mice.

Animals↗